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Results for “Lymphatic Metastasis”

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PubMed2003

Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats.

The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival. A number of clinical and experimental studies suggest that tumor-induced lymphangiogenesis driven by vascular endothelial growth factor (VEGF)-C- and/or VEGF-D-induced activation of VEGF receptor (VEGFR)-3 may promote metastasis to regional lymph nodes. Here we show that constitutive VEGF-C and VEGF-D expression by tumor cells of diverse origin grown in tissue culture does not correlate with metastatic potential in vivo. However, tumors derived from cell lines that do not constitutively express VEGF-C or VEGF-D in tissue culture can nevertheless express one or both of these factors. We demonstrate that both tumor and stromal cells can contribute to this expression, suggesting that tumor cell-host interactions determine tumor expression of VEGF-C and VEGF-D. Using immunocompetent rat mammary tumor models, we show in two ways that this expression can promote metastasis via the lymphatics. Firstly, ectopic expression of a soluble VEGFR-3 receptor globulin protein in MT-450 tumor cells that are highly metastatic via the lymphatics blocked VEGF-C and VEGF-D activity and suppressed metastasis formation in both the regional lymph nodes and the lungs. Secondly, ectopic expression in the weakly metastatic NM-081 cell line of a mutant form of VEGF-C that is only able to activate VEGFR-3 strongly promoted metastasis of these cells to the regional lymph nodes and lung. These data show that expression of VEGF-C and VEGF-D in tissue culture does not reflect expression in vivo and that activation of VEGFR-3 in the absence of VEGFR-2 activation is sufficient to promote tumor-induced lymphangiogenesis and metastasis, and they support the notion that blockade of VEGFR-3 activation will be useful as a novel form of cancer therapy.

Animals↗
PubMed2005

Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis.

Malignant tumours can spread to lymph nodes through lymphatic vessels. Recent studies show that tumours produce a range of growth factors that directly or indirectly stimulate lymphatic vessel growth (lymphangiogenesis) and lymphatic metastasis. These findings indicate that tumour lymphangiogenesis, similar to haemangiogenesis, is a complex process that is regulated by multiple growth factors. Understanding the underlying mechanisms by which tumours induce lymphangiogenesis might provide important information for the therapeutic intervention of metastatic spread.

Animals↗
PubMed2005

Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer.

BACKGROUND: Although abnormal hemostasis has been described in cancer patients, the precise association between the plasma fibrinogen level and lymphatic metastasis has not been reported in a large-scale clinical study. METHODS: Preoperative plasma levels of fibrinogen as well as C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were retrospectively examined in 649 patients who underwent surgery for gastric cancer, and the correlation between these factors and nodal status was evaluated. RESULTS: Plasma fibrinogen level in patients with gastric cancer showed a positive association with nodal classification (P < 0.0001). Hyperfibrinogenemia (>310 mg/dl) as well as high CEA (>5 ng/ml) and CRP (>0.3 mg/dl) showed a significant association with nodal metastasis in univariate analysis. Multivariate analysis revealed that hyperfibrinogenemia had an independent association with nodal metastasis (odds ratio, 2.004 (1.140-3.521); P = 0.0157), whereas CEA and CRP were not independent factors. Hyperfibrinogenemia showed an independent association even in advanced cancer [odds ratio 2.611 (1.404-4.854), P = 0.0024, n = 319]. When the 649 gastric cancers were classified into intestinal-type and gastric-type adenocarcinomas, plasma fibrinogen level was correlated with nodal metastasis only in the intestinal-type. CONCLUSIONS: Our results suggest that hyperfibrinogenemia may provide favorable circumstances for cancer cells to metastasize via the lymphatic system. Preoperative plasma fibrinogen level is a useful predictor of lymphatic metastasis in intestinal-type gastric cancer.

Adenocarcinoma↗
PubMed1993

[Lymphatic metastasis and cell adhesion, growth and growth inhibition].

Malignant tumor cells often metastasize to regional and distant lymph nodes. The mechanisms of lymphatic metastasis, however, have not been well understood. To investigate these mechanisms, we used mouse CS-21 malignant T lymphoma cells which form tumors at subcutaneous sites and metastasize to lymph nodes with a high incidence. In contrast, CS-21 cells do not metastasize to other organs following intravenous injection. CS-21 lymphoma cells continuously grew in vitro when the cells were cocultured with CA-12 stromal cells isolated from lymph nodes. However, when CS-21 cells were separated from the stromal cells, they underwent apoptosis which was characterized by nucleus condensation and DNA fragmentation. We have developed monoclonal antibodies against CS-21 cell surface molecules by intrasplenic injection of the cell membranes. Several clones of monoclonal antibodies were able to partially inhibit adhesion of CS-21 cells to a monolayer of CA-12 stromal cells. Treatment of CS-21 cells with the monoclonal antibodies which specifically bind to the cell surface components of M(r) -168K and -23K prevented the apoptosis of CS-21 cells after separation from the stromal cells. In the experiments using Transwell chambers we found that the growth of CS-21 cells was also supported by soluble factors secreted from CA-12 stromal cells. The secreted factors were, however, not sufficient to prevent CS-21 cell apoptosis. The result suggested that the stromal cells of lymph nodes play an important role in lymphatic metastasis of CS-21 lymphoma cells by cell-cell adhesion and secretion of soluble factors that prevent apoptosis of lymphoma cells and enhance their growth in concert.

Animals↗
PubMed1979

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.

Animals↗
PubMed2005

[Molecular biology approach to explain lymphatic metastasis].

The spread of tumor cells of solid tumors to the regional lymph nodes is an important step in the progression of the disease and also an important prognostic factor. While the significance of the prognostic value of the lymphatic progression had been detected long ago, only increased knowledge of the molecular anatomy and mechanisms involved in the lymphatic spread of tumor cells provided a beginning insight into the understanding of lymphatic metastasis. One group of important molecular factors consists of proteins produced by the tumor cells inducing a proliferation of lymphatic vessels into the primary tumor. The vascular endothelial growth factors have been identified as key factors in this process. In addition there are hints for the fact that chemokines, which are cytokine-like proteins taking part in the regulation of processes of inflammation, and their chemokine receptors control cellular key steps of lymphatic metastasis of tumor cells such as migration, proliferation, and invasion. In conclusion new data point to the possible inhibition of lymphatic spread by selective blockade of growth factor receptors or chemokine receptors. The growing insight into cellular understanding of the mechanisms involved in the metastasis of tumor cells into the lymphatics and lymph nodes will hopefully facilitate the development of new diagnostic and therapeutic tools in the treatment of cancer patients.

Animals↗
PubMedDate not supplied

The pattern of lymphatic metastasis of malignant tumors in the periorbital area.

BACKGROUND AND OBJECTIVES: The rarity of malignant tumors in the periorbital area makes it difficult to assess the patterns of lymphatic spread and to determine the optimal extent of treatment. The objective of this study was to analyze the patterns of lymphatic metastasis in malignant tumors arising from the periorbital area according to the primary site and to assess the optimal extent of surgical treatment for these tumors. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 8 patients with malignant tumors in the periorbital area from January 1997 to June 2002. The mean duration of follow-up was 27.5 months. Five primary tumors were located in the medial half of the periorbital area, 2 tumors in both medial and lateral halves, and 1 tumor in the lateral half. The pathological diagnoses were 3 squamous cell carcinomas, 2 adenoid cystic carcinomas, 2 sebaceous carcinomas, and 1 basal cell carcinoma. RESULTS: The lymphatic metastasis was observed in 4 of 8 patients who had a relatively large (> or =4 cm) primary tumor or poorly differentiated tumor. Four of 7 tumors involving the medial half of the periorbital area exhibited lymphatic spread to the periparotid lymph node and level II cervical lymph node groups. CONCLUSION: The results of this study suggest that more aggressive management of the parotid area is necessary in malignant tumors arising from the periorbital area, even in the medial half of the periorbital area.

Adult↗
PubMed2006

[Expression of Ezrin and E-cadherin in invasive ductal breast cancer and their correlations to lymphatic metastasis].

BACKGROUND & OBJECTIVE: Ezrin, a cytoskeleton linker protein, is actively involved in regulating the growth and metastasis of cancer cells. This study was performed to detect the expression of Ezrin and E-cadherin in primary invasive ductal breast cancer in order to evaluate their possible roles in lymphatic metastasis. METHODS: The expression of Ezrin and E-cadherin in 60 specimens of primary invasive ductal breast cancer (23 with metastasis, 37 without metastasis) was detected by SP immunohistochemistry. RESULTS: The abnormal expression rates of Ezrin and E-cadherin were significantly higher in the cases with metastasis than in the cases without metastasis (73.91% vs. 51.35%, P=0.039; 65.22% vs. 40.54%, P<0.001). The abnormal expression of Ezrin was positively correlated to that of E-cadherin (r=0.898, P=0.038). CONCLUSION: Ezrin and E-cadherin are closely related to invasion and metastasis of ductal breast cancer, suggesting that they are important tumor markers in predicting lymphatic metastasis of invasive ductal breast cancer.

Adult↗
PubMed2001

[Relationship among lymphatic metastasis, pericancerous lymphocytic reaction and dendritic cell infiltration in laryngeal carcinoma cells].

OBJECTIVE: To study the role and the clinical significance of dendritic cell infiltration against tumor cells in patients with laryngeal squamous cell carcinoma. METHODS: Immunohistochemical method using S-100 protein antibody was employed to detect dendritic cells (DC) on paraffin-embedded tissue sections from 23 patients with laryngeal squamous cell carcinomas. The relationships among the density of dendritic cell infiltration in laryngeal carcinomas and cervical lymphatic metastasis, pericancerous lymphocytic reaction and other clinicopathologic parameters were observed. RESULTS: The numbers of dendritic cells infiltrating among laryngeal carcinoma cells in patients with no cervical lymph metastasis was significantly larger than those with cervical lymphatic metastasis (t = 4.889, P < 0.01). Significant increase DC infiltration among laryngeal carcinoma cells was found in the group with intensively positive reaction of pericancerous lymphocyte than in the medium and weakly positive groups. The number of infiltrating dendritic cells in patients who had survived more than 5 years was significantly larger than those survived less than 5 years (t = 4.423, P < 0.01). The numbers of the infiltrating dendritic cells in patients with well-differentiated squamous cell carcinoma and poorly differentiated squamous cells carcinoma were 2.2 +/- 1.07 and 14.6 +/- 7.14 respectively, which were significantly different (q = 4.532, P < 0.05). CONCLUSION: The study showed that DC infiltration among laryngeal squamous carcinoma cells played an important role in the host immune reaction against tumor. It indicated that when the density of infiltrating DC is higher, the patients had less chance of cervical lymph metastasis and may have a longer survival time. There was a coordinative effect between DC infiltration in tumor cells and pericancerous lymphocyte reaction. Thus, the DC infiltration among laryngeal squamous cells could be used as an index of prognosis.

Aged↗
PubMed2001

Pathologic features of occult lymphatic metastasis in supraglottic carcinoma.

OBJECTIVE: To study the pathologic features of occult lymphatic metastasis in supraglottic carcinoma. METHODS: Serial sections of 153 neck dissection specimens in 100 patients with supraglottic carcinoma were evaluated under the microscope. RESULTS: In 100 patients, 38 had occult metastatic lymph nodes. 51 metastatic lymph nodes were found in pathology, and their sizes ranged from 0.5 cm to 2.6 cm (average 1.1 cm). The distribution of 51 lymph nodes was 1 in level I (2%), 37 in level II (73%), 12 in level III (24%), and 1 in level IV (2%). Among the 51 nodes, 21 (41%) were early stage, 18 (35%) were growth stage, 7 (14%) were tull stage, and 5 (10%) were extracapsular stage. The differentiation degree and appearance of supraglottic carcinoma was not directly related with occult metastasis. CONCLUSION: The occult metastatic rate of supraglottic carcinoma is high, and selective neck dissection may be necessary.

Adult↗
PubMed1999

[Pathologic feature of occult lymphatic metastasis in supraglottic carcinoma].

OBJECTIVE: To study the pathologic features of occult lymphatic metastasis in patients with supraglottic carcinoma and its implication in treatment. METHODS: Serial sections of 153 neck dissection specimens in 100 patients with supraglottic carcinoma were studied under microscope. RESULTS: Clinically negative nodes had been proved histologically positive in 58 specimens (38%) and 51 occult nodes, size ranged from 0.5 cm to 2.6 cm with average of 1.1 cm. The distribution of metastastic lymph nodes was 1 in level I (2%), 37 in level II (73%), 12 in level III(23%) and 1 in level IV(2%). Among the 51 nodes, 21(41%) were in early stage, 18 (35%) in growth stage, 7(14%) in full stage, 5(10%) were extracapsular. CONCLUSION: Occult metastasis rate of supraglottic carcinoma is as high as 38%, selective neck dissection is recommended for the surgical treatment of this disease.

Adult↗
PubMed2004

PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.

Cancer metastases are commonly found in the lymphatic system. Like tumor blood angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of several tumor-derived growth factors. Here we report that members of the PDGF family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF-BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.

Animals↗
PubMed2002

Lymphatic metastasis to the supraretrospinal recess in laryngeal squamous cell carcinoma.

In order to evaluate lymphatic metastasis to the supraretrospinal recess (SRSR) in laryngeal squamous cell carcinoma (SCC), we separately dissected SRSR lymph nodes and submitted them to pathological examination. Fifty-three lateral neck dissections (LNDs), 2 radical neck dissections (RNDs), and 19 modified RNDs were performed in 49 previously untreated patients with laryngeal SCC. The nodal status of the patients was N0 in 29 patients, N1 in 17, and N2 in 3. The neck was pathologically positive in both RNDs (100%), in 7 of 19 modified RNDs (37%), and in 7 of 53 LNDs (13%). No SRSR lymph nodes were positive in any of the dissection materials. No metastasis was found in the SRSR lymph nodes in the N0 necks treated with LND, and none was found even in N1 and N2 necks treated with RND or modified RND. We conclude that the SRSR may be left undissected during treatment of an N0 neck with LND so that accessory nerve dysfunction can be minimized and operative time can be saved.

Adult↗
PubMed2005

Screening differentially expressed genes in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.

AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis. METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed. RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes. CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.

Animals↗
PubMed2005

[Pathological feature and management of occult lymphatic metastasis in supraglottic carcinoma].

OBJECTIVE: To study the pathologic feature and management methods of occult lymphatic metastasis in patients with supraglottic carcinoma. METHODS: The following are criteria of patients selection: (1) Supraglottic squamous cell carcinoma; (2) Clinical N0M0; (3) no preoperative radiotherapy and (or) chemotherapy. Thirty patients were recruited, male 19 cases, female 11; age: 40 - 72yr, average 54.8yr; T2 8 cases, T3 18, T4 4 (by UICC 1997). Ipsilateral supraomohyoid neck dissections were performed in all cases. Lymph nodes were studied histologically according to the levels of dissection. RESULTS: Six of 30 cases were positive nodes histologically in first operation, 3 were occurrence neck metastasis in opposite side during follow ups. Occult metastasis rate was 20% (6/30) ipsilaterdly and 10% contralaterally. 527 lymph nodes were collected in all of 30 patients, average 17.6 nodes in every side neck. Ten positive lymph nodes histologically were harvested. The distribution of metastatic lymph nodes was 9 in level II, 1 in level III, no in level I. N0 recurrence in larynx and (or) at the neck after dissection. Two years survival rates was 86.7% (26/30) without tumor. CONCLUSION: Occult metastasis rate of supraglottic carcinoma is as high as 30%. The selective lateral neck dissection of level II, III and occasionally, level IV was recommended.

Adult↗
PubMed2006

Functional expression of CXC chemokine recepter-4 mediates the secretion of matrix metalloproteinases from mouse hepatocarcinoma cell lines with different lymphatic metastasis ability.

CXC chemokine recepter-4 (CXCR4) and its ligand, stromal cell-derived factor-1alpha (SDF-1alpha) have been implicated in the organ-specific metastasis of several malignancies. Hca-F and its syngeneic cell line Hca-P are mouse hepatocarcinoma cell lines with high and low potential of lymphatic metastasis, respectively. Previous studies showed that the secretion of matrix metalloproteinases (MMPs) associated with the metastatic ability of Hca-F and Hca-P cell line depending on the lymph node environment. However, the mechanism of this process has remained unclear. This study investigated the roles of CXCR4 on Hca-F cell and SDF-1alpha of lymph node in lymphatic metastasis. The RT-PCR and Flow cytometry analysis results show that Hca-F cells express higher level CXCR4 mRNA and cell-surface CXCR4 protein, as compared with Hca-P cells. Treatment of recombinant SDF-1alpha proteins induced greater amount of calcium-flux in Hca-F cells than that in Hca-P cells, demonstrating higher functional CXCR4 expression on Hca-F cells than that on Hca-P cells. Furthermore, both the cell-free extratcs of lymph node and recombinant SDF-1alpha proteins induced secretions of active MMP-9 and MMP-2 from Hca-F cells in vitro. But those secretions were significantly reduced by blockade of cell surface CXCR4 with rabbit anti-mouse CXCR4 polyclonal antibody (pAb) and neutralization of SDF-1alpha in lymph node extracts with rabbit anti-mouse SDF-1alpha pAb as well. These results suggest that the CXCR4/SDF-1alpha system mediates active MMP-9 and MMP-2 secretion from Hca-F and Hca-P cells, which facilitates lymphogenous metastasis of those cells consequently.

Animals↗