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Marie-Christine Rio

Publications and source records attributed to Marie-Christine Rio.

At least 19 recordsLinked to original sources
PubMed2006

Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification.

In the present study the cytotoxic activity of aloin, a natural anthracycline from Aloe plant, is reported against two human breast cancer cell lines; without (MCF-7) and with (SKBR-3) erbB-2-topoIIalpha coamplification. MCF-7cell line was shown to be more sensitive to aloin than SKBR-3 demonstrated by MTT and clonogenic assays, from which IC50 and 50% ICF values are reported to be 60 microg/ml, respectively, in the former cell line and as high as 150 and 80 microg/ml, respectively, in the latter, which are still far below the maximum tolerated dose of the compound. The effect of aloin is suggested to be brought about by more than one mechanism depending on the dose level and tumor phenotype. This was demonstrated by flow cytometric analysis, fluorescence microscopy and western blot analysis, which revealed that aloin at higher concentrations caused a reduction in the proportion of cells undergoing mitosis by induction of apoptosis, inhibition of topo II alpha protein expression and downregulation of cyclin B1 protein expression in MCF-7 cell line, whereas erbB-2 protein expression was not affected. Topo IIalpha protein expression was mildly downregulated in SKBR-3 cell line at higher concentrations only.

Antigens, Neoplasm↗
PubMed2006

Serum biomarkers for detection of breast cancers: A prospective study.

Using surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF), Li et al. [Clin Chem 48(8): 1296-1304, 2002] identified 3 serum biomarkers, BC1 (4.3 kDa), BC2 (8.1 kDa) and BC3 (8.9 kDa), whose combination significantly detects breast cancer patients from non-cancer controls. This work aimed to validate these biomarkers in an independent prospective study. We screened 89 serum samples including 49 breast cancers at pT1-4N0M0 (n = 23), pT1-4N1-3M0 (n = 17) or pT1-4N0-3M1 (n = 9) stages, 13 benign breast diseases and 27 healthy women. The BC2 biomarker significance was not recovered. However, we found 2 peaks that we named BC1a (4286 Da) and BC1b (4302 Da), that could correspond to Li's BC1 since they significantly decrease in breast cancers (p < 0.00007 and p < 0.0002, respectively). Similarly, BC3a (8919 Da) and BC3b (8961 Da) are significantly increased in breast cancers (p < 0.02 and p < 0.0002, respectively) and could correspond to the Li's BC3. For each biomarker we defined stringent (no errors) and flexible (less than 10% errors) cut-off values and tested the power of the combined BC1a/BC1b/BC3a/BC3b stringent and flexible profiles to discriminate breast cancers. They identified 33% and 45% cancers, respectively. Applied to the same series, Ca 15.3 test identified 22% patients. Interestingly, in association with the BC1a/BC1b/BC3a/BC3b profiles, Ca 15.3 improved the number of detected cancers indicating that it is an independent parameter. Collectively, our data partially validate those of Li's study and confirm that the BC1 and BC3 biomarkers are helpful for breast cancer diagnosis.

Adenocarcinoma, Mucinous↗
PubMed2005

Overexpression of the small transmembrane and glycosylated protein SMAGP supports metastasis formation of a rat pancreatic adenocarcinoma line.

Small cell transmembrane and glycosylated protein (SMAGP) was recently identified in the metastasizing rat pancreatic adenocarcinoma line BSp73ASML. SMAGP, an evolutionary conserved transmembrane protein, is expressed on lateral epithelial cell membranes. SMAGP expression was restricted to or was upregulated in several metastasizing as compared to nonmetastasizing human and rat tumor lines. In contrast to nontransformed tissue, SMAGP was mainly expressed in the cytoplasm, as has already been described for high-grade human colorectal cancer. This raised the question on the impact of SMAGP on tumor progression. To answer the question, metastasis formation was evaluated in the nonmetastasizing rat pancreatic adenocarcinoma subline BSp73AS (AS), which was stably transfected with SMAGP cDNA (AS-SMAGP). Cytoplasmic SMAGP expression promoted cell agglomeration, but inhibited tumor cell proliferation, adhesion to and migration toward vitronectin and matrigel invasion, which was accompanied by a failure of actin reorganization. AS-SMAGP clones strongly promoted metastasis formation by dislodgment of normal tissue; 82% of rats developed lymph node metastasis as compared to 22% of rats receiving AS or mock-cDNA-transfected AS cells. The incidence of lung metastasis was increased from 6% in AS to 98% in AS-SMAGP tumor-bearing rats. Thus, SMAGP strongly promotes tumor progression. This likely is due to redistribution from the plasma membrane into the cytoplasm. SMAGP redistribution does not only facilitate tumor cell detachment from neighboring cells and the extracellular matrix, but obviously contributes actively by a not yet defined mechanism to tumor cell agglomeration and capillary plugging.

Adenocarcinoma↗
PubMed2005

Towards an inline reconstruction architecture for micro-CT systems.

Recent developments in micro-CT have revolutionized the ability to examine in vivo living experimental animal models such as mouse with a spatial resolution less than 50 microm. The main requirements of in vivo imaging for biological researchers are a good spatial resolution, a low dose induced to the animal during the full examination and a reduced acquisition and reconstruction time for screening purposes. We introduce inline acquisition and reconstruction architecture to obtain in real time the 3D attenuation map of the animal fulfilling the three previous requirements. The micro-CT system is based on commercially available x-ray detector and micro-focus x-ray source. The reconstruction architecture is based on a cluster of PCs where a dedicated communication scheme combining serial and parallel treatments is implemented. In order to obtain high performance transmission rate between the detector and the reconstruction architecture, a dedicated data acquisition system is also developed. With the proposed solution, the time required to filter and backproject a projection of 2048 x 2048 pixels inside a volume of 140 mega voxels using the Feldkamp algorithm is similar to 500 ms, the time needed to acquire the same projection.

Algorithms↗
PubMed2005

Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer cell-adipocyte interaction/crosstalk at the tumor invasive front.

The initial invasive processes during cancer development remain largely unknown. Stromelysin-3/matrix metalloproteinase 11 (ST3/MMP11) is associated with tumor invasion and poor prognosis. We present novel evidence that adipocytes present at human breast tumor invasive front are induced by cancer cells to express ST3. Using mouse syngeneic model, light and electron microscopy showed that in ST3-deficient mice but not in wild-type mice, forced cancer cell-adipocyte interaction/crosstalk results in adipocyte membrane alteration, allowing cancer cell fat infiltration and death. Thus, adipocytes are involved in initial cancer cell survival into connective tissue, and this effect is ST3 mediated. This suggested that ST3 might play a role in adipocyte metabolism. Accordingly, ST3-deficient mice exhibited fat excess and increased mRNA levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and adipocyte protein 2 (aP2) adipogenic markers, indicating that, in vivo, ST3 negatively regulates fat homeostasis. Moreover, ST3-deficient mouse embryonic fibroblasts exhibited a dramatic enhanced potential to differentiate into adipocytes associated with increased PPARgamma and aP2 expression, and recombinant ST3 treatment reverted their differentiation. Thus, in vitro, ST3 reduces adipocyte differentiation in an autocrine manner. High fibroblasts/adipocytes ratio is a stroma feature, and peritumoral fibroblast origin remains debated. Our results support the concept that invading cancer cells aberrantly restore the negative ST3 function on adipogenesis into proximal adipocytes/preadipocytes, leading to the accumulation/maintenance of a particular peritumoral fibroblast subpopulation. Accordingly, in human breast tumors, we observed that ST3-expressing peritumoral fibroblasts are distinct from alpha-smooth muscle actin-expressing myofibroblasts. This constitutes the first report of implication of a MMP in cancer cell-adipocyte interaction/crosstalk during early steps of connective tissue invasion.

Adipocytes↗
PubMed2005

Dosing and scheduling influence the antitumor efficacy of a phosphinic peptide inhibitor of matrix metalloproteinases.

The in vivo disposition and antitumor efficacy of a newly developed phosphinic matrix metalloproteinase inhibitor (RXP03) were examined. RXP03 potently inhibits MMP-11, MMP-8 and MMP-13, but not MMP-1 and MMP-7. Twenty-four hours after i.p. injection into mice, most of the RXP03 was recovered intact in plasma, feces (biliary excretion) and tumor tissue. Pharmacokinetic parameters indicated that, after an i.p. dose of 100 microg/day, the plasma concentration of RXP03 over 24 hr remained higher than the Ki values determined for MMP-11, MMP-8 and MMP-13. Efficacy of RXP03 on the growth of primary tumors induced by s.c. injection of C(26) colon carcinoma cells in mice was observed to depend both on RXP03 doses and treatment schedules. Tumor volumes in mice treated for 18 days with 50, 100 and 150 microg/day of RXP03 were decreased compared with control tumor volumes, 100 microg/day being the most effective dose. Treatment at higher dose (600 microg/day) did not significantly reduce the tumor size as compared to control. Short treatments with RXP03 100 microg/day, 3 to 7 days after C(26) inoculation, were more effective on tumor growth than continuous treatment over 18 days. Strikingly, RXP03 treatment started 6 days after the C(26) injection and continued until day 18 led to stimulation of tumor growth, as compared to control. These paradoxical effects, depending on the RXP03 treatment schedule, underline the need to define carefully the spatiotemporal function of each MMP at various stages of tumor growth to achieve optimal therapeutic effects by MMP inhibitor treatment.

Alkylating Agents↗
PubMed2005

Functional characterization of the MENTAL domain.

Human metastatic lymph node (MLN) 64 is composed of two conserved regions. The amino terminus contains a conserved membrane-spanning MENTAL (MLN64 NH(2)-terminal) domain shared with an unique protein called MENTHO (MLN64 NH(2)-terminal domain homologue) and targets the protein to late endosome. The carboxyl-terminal domain is composed of a cholesterol binding steroidogenic acute regulatory-related lipid transfer domain exposed to the cytoplasm. MENTHO overexpression leads to the accumulation of enlarged endosomes. In this study, we show that MLN64 overexpression also induces the formation of enlarged endosomes, an effect that is probably mediated by the MENTAL domain. Using an in vivo photocholesterol binding assay, we find that the MENTAL domain of MLN64 is a cholesterol binding domain. Moreover, glutathione S-transferase pull-down or co-immunoprecipitation experiments demonstrate that this domain mediates homo- and hetero-interaction of MLN64 and MENTHO. In living cells, the expression of paired yellow fluorescent and cyan fluorescent fusion proteins show MENTHO homo-interaction and its interaction with MLN64. These data indicate that within late-endosomal membranes, MLN64 and MENTHO define discrete cholesterol-containing subdomains. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s).

Carrier Proteins↗
PubMed2005

Improvement in intramammary sentinel lymph node removal using a novel prototype hand held probe during breast conservative surgery.

Intramammary sentinel lymph node excision during breast conservative surgery was performed, in this case report, using a prototype intraoperative gamma probe. In contrast to the four axillary sentinel lymph nodes that were subnormal, the excised intramammary sentinel lymph node was massively invaded by cancer cells. Therefore this finding had profound implication for the staging of the tumor and for treatment selection. This case report illustrates that an efficient intraoperative gamma probe is useful to locate and remove intramammary sentinel lymph node in breast cancer patients treated with breast conservation.

Breast Neoplasms↗
PubMed2005

[Trefoil factor 1 (pS2/TFF1), a peptide with numerous functions].

The trefoil factor (TFF) family includes three members : TFF1 also called pS2, TFF2 or spasmolytic peptide (SP) and TFF3 or intestinal trefoil factor (ITF). TFFs are associated with mucin-secreting epithelial cells and play a crucial role in mucosal defense and healing. In case of mucosa aggression (due to bacteria, virus or medication), inflammatory diseases and ulcerous pathology, they are involved in epithelium restitution and regeneration. In comparison with the other TFFs, pS2/TFF1 has particular functions. Notably, it acts like a suppressor gene for gastric tumors. Evidence of pS2/TFF1 overexpression has been found in a range of carcinomas (breast, bowel, prostate, pancreas, thyroid, lung...). In breast cancer, pS2/TFF1 overexpression contributes to a favorable prognosis. Moreover, it is a predictive factor of hormonotherapy response.

Adenoma↗
PubMed2004

Spatial and temporal distribution of the traf4 genes during zebrafish development.

The tumor necrosis factor-associated factor 4 (TRAF4) is a particular member of the TRAF protein family since it is not involved in the Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1) signaling pathways. In the present study, we cloned two zebrafish orthologs of the human traf4, traf4a and traf4b, which are the first TRAFs described in zebrafish. During embryogenesis, traf4b expression is present in a weak ubiquitous manner. In contrast, traf4a exhibits a highly specific expression pattern in the sensorial and neural cells, and the somites of embryos. This gene is tightly regulated during embryogenesis. Together, our data show that traf4 is conserved during evolution, and traf4a is the zebrafish ortholog of traf4.

Amino Acid Sequence↗
PubMed2004

Association of the breast cancer protein MLN51 with the exon junction complex via its speckle localizer and RNA binding module.

MLN51 is a nucleocytoplasmic shuttling protein that is overexpressed in breast cancer. The function of MLN51 in mammals remains elusive. Its fly homolog, named barentsz, as well as the proteins mago nashi and tsunagi have been shown to be required for proper oskar mRNA localization to the posterior pole of the oocyte. Magoh and Y14, the human homologs of mago nashi and tsunagi, are core components of the exon junction complex (EJC). The EJC is assembled on spliced mRNAs and plays important roles in post-splicing events including mRNA export, nonsense-mediated mRNA decay, and translation. In the present study, we show that human MLN51 is an RNA-binding protein present in ribonucleo-protein complexes. By co-immunoprecipitation assays, endogenous MLN51 protein is found to be associated with EJC components, including Magoh, Y14, and NFX1/TAP, and subcellular localization studies indicate that MLN51 transiently co-localizes with Magoh in nuclear speckles. Moreover, we demonstrate that MLN51 specifically associates with spliced mRNAs in co-precipitation experiments, both in the nucleus and in the cytoplasm, at the position where the EJC is deposited. Most interesting, we have identified a region within MLN51 sufficient to bind RNA, to interact with Magoh and spliced mRNA, and to address the protein to nuclear speckles. This conserved region of MLN51 was therefore named SELOR for speckle localizer and RNA binding module. Altogether our data demonstrate that MLN51 associates with EJC in the nucleus and remains stably associated with mRNA in the cytoplasm, suggesting that its overexpression might alter mRNA metabolism in cancer.

Amino Acid Sequence↗
PubMed2004

Regulation of cell migration and survival by focal adhesion targeting of Lasp-1.

Large-scale proteomic and functional analysis of isolated pseudopodia revealed the Lim, actin, and SH3 domain protein (Lasp-1) as a novel protein necessary for cell migration, but not adhesion to, the extracellular matrix (ECM). Lasp-1 is a ubiquitously expressed actin-binding protein with a unique domain configuration containing SH3 and LIM domains, and is overexpressed in 8-12% of human breast cancers. We find that stimulation of nonmotile and quiescent cells with growth factors or ECM proteins facilitates Lasp-1 relocalization from the cell periphery to the leading edge of the pseudopodium, where it associates with nascent focal complexes and areas of actin polymerization. Interestingly, although Lasp-1 dynamics in migratory cells occur independently of c-Abl kinase activity and tyrosine phosphorylation, c-Abl activation by apoptotic agents specifically promotes phosphorylation of Lasp-1 at tyrosine 171, which is associated with the loss of Lasp-1 localization to focal adhesions and induction of cell death. Thus, Lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ECM proteins.

Actins↗
PubMed2004

SMAGP, a new small trans-membrane glycoprotein altered in cancer.

Using the Affymetrix array technology, we previously identified an EST strongly expressed in several metastatic cell lines. In the present study, we cloned the corresponding cDNA that encodes a new glycoprotein composed of 97 amino acids and containing a trans-membrane domain. Therefore, we named it SMAGP for Small trans-Membrane And Glycosylated Protein. SMAGP is strongly conserved during evolution. It is expressed by normal epithelia of various organs, the protein being notably localized to the lateral face of the plasma membrane of cohesive well-polarized epithelial cells. In addition, SMAGP contains binding domains for the protein 4.1 and the PDZ domain of MAGUK proteins. Similar protein features are observed in several cell-surface proteins involved via ternary complexes in intercellular processes leading to cytoskeleton assembly as well as intracellular signalling. Thus, SMAGP might similarly be involved in a scaffolding protein complex, and therefore participate in the epithelium organization or in subsequent functions. Immunohistochemical data obtained using human breast, colon and lung cancer samples sustain this hypothesis since they showed that, in both primary tumours and metastases, reduced expression and/or cytoplasmic redistribution of SMAGP is superimposable with low histological tumour differentiation features, namely a lack of epithelial cell polarity and disorganized tissue phenotype.

Amino Acid Sequence↗
PubMed2004

Urinary pS2/TFF1 levels in the management of hormonodependent breast carcinomas.

pS2/TFF1 overexpression in breast carcinomas correlates with response to hormonotherapy. We evaluated the clinical relevance of urinary pS2/TFF1 in breast cancer patients. In healthy controls (100 cases), it represents an individual and relatively stable parameter. Although 24 out 83 pre-operative breast cancer patients showed elevated levels, both the sensitivity and specificity of the test were too low for breast cancer screening. However, neoadjuvant hormonotherapy decreased pS2/TFF1 levels in nine out of 20 patients. Furthermore, among 22 patients receiving long-term adjuvant hormonotherapy, four exhibited elevated levels, two of them at the time of relapse. Thus, urinary pS2/TFF1 quantification might be suitable as an in vivo diagnosis for tumor hormonodependency, and disease follow-up during hormonotherapy.

Breast Neoplasms↗
PubMed2004

Profiling trefoil factor family (TFF) expression in the mouse: identification of an antisense TFF1-related transcript in the kidney and liver.

The expression of the trefoil factor family (TFF) genes (TFF1, TFF2, and TFF3) was systematically analyzed in 18 different organs from male or female mice using RT-PCR analysis. The expression patterns showed some gender-specific differences, e.g., TFF3 transcripts in the urinary bladder and liver. Furthermore, the murine expression profile differed from that in human, e.g., in the respiratory tract and uterine cervix. As a hallmark, an aberrant TFF1-related transcript was detected specifically in the kidney and liver of several mouse strains. Molecular characterization of this rare 1.8kb long transcript from the kidney clearly revealed that its 3' region originated from the antisense strand of the TFF1 locus containing particularly large parts of the antisense strands of introns 1 and 2. Homology searches using various databases revealed that this antisense TFF1-related transcript is subject of intense alternative splicing and no protein product encoded by this antisense TFF1-related transcript could be identified. Although the function of this transcript is not known currently, we can speculate that this antisense TFF1-related transcript might have a gene silencing effect particularly on TFF1 expression in the murine kidney and liver.

Amino Acid Sequence↗
PubMed2003

Dual stromelysin-3 function during natural mouse mammary tumor virus-ras tumor progression.

In human carcinomas, stromelysin-3/matrix metalloproteinase 11 (ST3, MMP11) expression by nonmalignant fibroblastic cells located in the immediate vicinity of cancer cells is a bad prognostic factor. Using mouse models of primary tumors, it has been demonstrated that ST3 is a key player during local invasion, favoring cancer cell survival in connective tissue through an antiapoptotic function. To investigate the ST3 impact on additional phases of cancer cell invasion, we developed mammary gland cancer prone MMTV-ras transgenic mice in wild-type (ras+/+;ST3+/+) or ST3-deficient (ras+/+;ST3-/-) genotype and studied their whole natural cancer history. The tumor-free survival and delay between the first ras oncogenic hit and primary tumor appearance increased in ras+/+;ST3-/- mice (P < 0.000001 and <0.0000007, respectively). A systematic search for occult primary tumors and metastases revealed, in addition to a lower total number and size of primary tumors (P < 0.02), an unexpected higher number of metastases (P < 0.01) in ras+/+;ST3-/- mice. Moreover, for a similar number and size of primary invasive tumors, ras+/+;ST3-/- mice developed more metastases, indicating that the cancer cells evolving in ST3-deficient stroma have an increased potential to hematogenous dissemination. We conclude that the ST3 microenvironment is a consistently active partner of invading cancer cells but that its function differs throughout cancer progression, being tumor enhancer or repressor in processes leading to local or distal invasion. Such a dual effect for an MMP might shed light, at least partially, for the absence of survival benefit for patients included in anti-MMP clinical trials.

Animals↗
PubMed2003

Cyclooxygenase-2 expression and effect of celecoxib in gastric adenomas of trefoil factor 1-deficient mice.

Expression of cyclooxygenase-2 (Cox-2) is elevated in gastric adenocarcinomas and precursor lesions leading to this disease. Mice deficient for trefoil factor 1 (TFF1) develop a pyloric adenoma with full penetrance. Because inhibition of Cox-2 suppresses tumor growth in several animal models, we studied expression of Cox-2 and effect of a selective Cox-2 inhibitor celecoxib in gastrointestinal tissues of the TFF1-deficient mice. Cox-2 mRNA and protein were strongly expressed in the pyloric adenomas of the TFF1(-/-) mice as detected by in situ hybridization and immunohistochemistry. Nonneoplastic gastrointestinal tissues of wild-type or TFF1(-/-) mice expressed low or nondetectable levels of Cox-2. Celecoxib (1600 ppm p.o. for 3 months) caused ulceration and inflammation of the adenoma in all treated TFF1(-/-) mice (n = 7). This effect of the drug was adenoma specific, because no histological alterations were observed in the non-neoplastic gastric or intestinal tissues in the TFF1(-/-) or wild-type mice receiving the drug treatment. All untreated TFF1(-/-) mice had an adenoma (n = 7), but none demonstrated the combination of ulceration and inflammation. Our data show that Cox-2 is expressed in gastric adenomas of the TFF1(-/-) mice and suggest that inhibition of Cox-2 disturbs the integrity of the adenoma by promoting ulceration and inflammation. These findings support the effort to initiate clinical studies to investigate the effect of Cox-2 inhibitors as a chemotherapeutic modality for dysplasias of the stomach.

Adenoma↗