Biomedical subjects

Jingcheng Wang

Publications and source records attributed to Jingcheng Wang.

6 recordsLinked to original sources

PubMed2007

Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells.

Early B lymphopoiesis in mammals is induced within the bone marrow (BM) microenvironment, but which cells constitute this niche is not known. Previous studies had shown that osteoblasts (OBs) support hematopoietic stem cell (HSC) proliferation and myeloid differentiation. We now find that purified primary murine OBs also support the differentiation of primitive hematopoietic stem cells through lymphoid commitment and subsequent differentiation to all stages of B-cell precursors and mature B cells. Lin(-)Sca-1(+)Rag-2(-) BM cell differentiation to B cells requires their attachment to OBs in vitro, and this developmental process is mediated via VCAM-1, SDF-1, and IL-7 signaling induced by parathyroid hormone (PTH). Addition of cytokines produced by nonosteoblastic stromal cells (c-Kit ligand, IL-6, and IL-3) shifted the cultures toward myelopoiesis. Confirming the role of OBs in B lymphopoiesis, we found that selective elimination of osteoblasts in Col2.3Delta-TK transgenic mice severely depleted pre-pro-B and pro-B cells from BM, preceding any decline in HSCs. Taken together, these results demonstrate that osteoblasts are both necessary and sufficient for murine B-cell commitment and maturation, and thereby constitute the cellular homolog of the avian bursa of Fabricius.

Animals↗

PubMed2005

Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts.

Osteoblasts constitute part of the stromal cell support system in marrow for hematopoiesis, however little is known as to how they interact with hematopoietic stem cells (HSCs). In vitro studies have demonstrated that the survival of HSCs in co-culture with osteoblasts requires intimate cell-to-cell contact. This suggests that the osteoblast-derived factor(s) that supports stem cell activities are produced in very small quantities, are rapidly turned over, may be membrane-anchored and/or require the engagement of cell-cell adhesion molecules that are yet to be determined. In the present report we found that the survival of hematopoietic progenitor cells on osteoblasts is dependent upon the engagement of VLA-4 (alpha4beta1) and VLA-5 (alpha5beta1) receptors using function blocking antibodies. Cell-to-cell contact is required to support progenitor activity, but can be replaced if receptor-ligand engagement of the VLA-4 and LFA-1 complexes is provided through the use of recombinant ligands (fibronectin, ICAM-1, VCAM-1). Moreover, once these receptors were engaged, conditioned medium derived from HSCs grown on osteoblast ligands supported significantly greater hematopoietic progenitors in vitro than did osteoblast-conditioned or HSC-conditioned medium alone. While the molecules present in the co-cultured medium remain to be identified, the data suggest that hematopoietic cells cooperate with osteoblasts to assemble the various marrow microenvironments by directing the synthesis of osteoblast-derived cytokines to improve HSC survival.

Adult↗

PubMed2004

Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo.

UNLABELLED: To delineate the role of SDF-1 and CXCR4 in metastatic prostate cancer (CaP), positive correlations were established between SDF-1 levels and tumor metastasis. Neutralization of CXCR4 limited the number and the growth of intraosseous metastasis in vivo. Together, these in vivo metastasis data provide critical support that SDF-1/CXCR4 plays a role in skeletal metastasis. INTRODUCTION: Previously we determined that the stromal-derived factor-1 (SDF-1)/CXCR4 chemokine axis is activated in prostate cancer (CaP) metastasis to bone. To delineate the role of SDF-1/CXCR4 in CaP, we evaluated SDF-1 levels in a variety of tissues and whether neutralization of SDF-1 prevented metastasis and/or intraosseous growth of CaPs. MATERIALS AND METHODS: SDF-1 levels were established in various mouse tissues by ELISA, immunohistochemistry, and in situ hybridization. To assess the role of SDF-1/CXCR4 in metastasis, bone metastases were established by administering CaP cells into the left cardiac ventricle of nude animals in the presence or absence of neutralizing CXCR4 antibody. The effect of SDF-1 on intraosseous growth of CaP cells was determined using intratibial injections and anti-CXCR4 antibodies and peptides. RESULTS: There was a positive correlation between the levels of SDF-1 and tissues in which metastatic CaP lesions were observed. SDF-1 levels were highest in the pelvis, tibia, femur, liver, and adrenal/kidneys compared with the lungs, tongue, and eye, suggesting a selective effect. SDF-1 staining was generally low or undetectable in the center of the marrow and in the diaphysis. SDF-1 mRNA was localized to the metaphysis of the long bones nearest to the growth plate where intense expression was observed near the endosteal surfaces covered by osteoblastic and lining cells. Antibody to CXCR4 significantly reduced the total metastatic load compared with IgG control-treated animals. Direct intratibial injection of tumor cells followed by neutralizing CXCR4 antibody or a specific peptide that blocks CXCR4 also decreased the size of the tumors compared with controls. CONCLUSIONS: These data provide critical support for a role of SDF-1/CXCR4 in skeletal metastasis. Importantly, these data show that SDF-1/CXCR4 participate in localizing tumors to the bone marrow for prostate cancer.

Amino Acids↗

PubMed2003

Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo.

Human prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high-density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post-transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4-2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may 'home' to bone, and the mechanisms that may account for their growth in selected end organs.

Adult↗

PubMed2003

Immunoglobulin profiles in a murine intermediate host model of resistance for Echinococcus granulosus infection.

We have shown previously that primary infection of Chinese Kunming (CKM) mice with Echinococcus granulosus oncospheres is protective against subsequent challenge. Nine groups of mice were infected with the oncospheres of E. granulosus by different routes (intraperitoneal, subcutaneous or intravenous injection). After infection, serum was collected after different periods of time and serum antibodies were tested by ELISA against oncospheral proteins and hydatid cyst fluid antigens. The results indicated that CKM mice produced low levels of antibodies before a secondary challenge infection given 3 weeks later by a different route. Most mice did not evoke significant antibody responses against oncospheral antigens until 5 weeks after infection. The level of IgG, especially IgG1 against oncospheral antigens increased from week 4 post-infection (p.i.), to a maximum at week 9 p.i. In addition, antibodies against hydatid cyst fluid antigens increased at the same time as the recognition of oncospheral antigens. Immunoblots using hydatid cyst fluid showed that the first antigen that was recognized - an 8-kDa protein, possibly the smallest subunit of Antigen B - appeared 5-6 weeks p.i. and reactivity to this molecule was intensive at week 9 p.i. The results suggest that protection against secondary infection was not principally antibody-mediated during the initial phases of infection, when cellular immune responses may play a pivotal role in the protective mechanism.

Animals↗

PubMedDate not supplied

Expression of the chemokine receptor CCR7 in prostate cancer presenting with generalized lymphadenopathy: report of a case, review of the literature, and analysis of chemokine receptor expression.

PURPOSE: Generalized lymphadenopathy is a rare presentation of prostate cancer. We report a case and review reported cases in the literature. Because of the association of chemokine receptor expression with specific metastatic patterns, we tested for expression of chemokine receptors known to mediate migration to lymph nodes. METHODS: We performed a MEDLINE (National Library of Medicine, Bethesda, MD) database search for case reports during the last 32 years using "prostate cancer," "lymphadenopathy," "metastatic to lymph nodes," and "mimicking lymphoma" as keywords. Expression of the CXCR4 and CCR7 chemokine receptors was assessed by immunohistochemistry. Laser capture microdissection and reverse transcription polymerase chain reaction for CXCR4 were used to exclude nonspecific binding. RESULTS: Of 153 patients with prostate cancer presenting with lymphadenopathy (LAD) described in the literature, 67 (44%) presented with supraclavicular adenopathy, 29 (19%) retroperitoneal, 22 (14%) mediastinal, 15 (10%) cervical, 9 (6%) inguinal, and 2 (1%) axillary LAD. Only 9 patients presenting with generalized LAD have been previously reported. Monoclonal antibodies to CCR7 showed intense staining in the patient's tumor epithelium. Little or no staining was observed for CXCR4. Reverse transcription polymerase chain reaction for chemokine receptors on ribonucleic acid (RNA) recovered from the patient's sample failed to express messenger RNA for CXCR4 but did express messenger RNA for CCR1, CCR4, and CCR5. CONCLUSIONS: Prostate cancer may present on rare occasions with generalized adenopathy. Variable expression of chemokine receptors may be associated with organ specific patterns of metastasis. In this case, expression of CCR7 may have accounted for the unusual predilection of this patient's prostate cancer for lymph nodes.

Adult↗