Biomedical subjects

R Kannagi

Publications and source records attributed to R Kannagi.

203 records · Page 12Linked to original sources

PubMedDate not supplied

Corticosteroids and medroxyprogesterone acetate inhibit the induction of E-selectin on the vascular endothelium by MDA-MB-231 breast cancer cells.

The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between breast cancer cells and vascular endothelial cells in the expression of E-selectin, and the effect of corticosteroids or medroxyprogesterone acetate (MPA) on such interaction. An MDA-MB-231 cell line, derived from human breast cancer induced E-selectin on the cell surface of human umbilical vascular endothelial cells. This induction was enhanced with a supplement of mononuclear cells of peripheral blood added to the culture medium. Corticosteroids and MPA blocked the induction of E-selectin proportional to concentration. Anti-IL-1 beta, but not anti-IL1 alpha or- TNF a, antibodies blocked induction. These findings suggest that MDA-MB-231 cells induce expression of E-selectin on vascular endothelium by releasing IL-1 beta directly or indirectly, but this induction is blocked by corticosteroids and MPA. Corticosteroids and MPA may inhibit cancer metastasis by blocking E-selectin expression on the vascular endothelium.

Antibodies, Monoclonal↗

PubMedDate not supplied

The association of metastasis with the expression of adhesion molecules in cell lines derived from human gastric cancer.

Peritoneal dissemination and hepatic metastasis commonly occur after patients with gastric cancer have undergone surgery. The presence of metastasis after surgery is sure to affect the prognosis of patients with gastric cancer. We conducted in vitro and in vivo studies to assess the role of adhesion molecules in this process, using 2 cell lines derived from human gastric cancer. Although both cell lines expressed several adhesion molecules to varying degrees, NUGC-4 cells, which disseminated early after inoculation into the abdominal cavity of nude mice accompanied by the formation of bloody ascitic fluid, predominantly expressed CD44H. However, MKN74 cells, which demonstrated hematogenous metastasis in the liver after inoculation into the spleen of nude mice, strongly expressed the sialyl Lewis(x) antigen (s-Le(x)), but did not express CD44H at all. When the binding of both these cancer cells to human umbilical vein endothelial cells was examined it was found that MKN74 cells adhered more strongly than NUGC-4 cells. The adhesion of cancer cells to endothelial cells was inhibited by treatment with antibodies against s-Le(x) and E-selectin. In the liver metastasis model of nude mice, treatment with anti-s-Le(x) antibodies significantly inhibited the development of MKN74 cell liver metastasis, both in the number of tumor nodules and in liver weight. NUGC-4 cells adhered to monolayers of mesothelial cells more strongly than MKN74 cells. The adhesion of NUGC-4 cells to these cells was partially inhibited by antibodies either against CD44H or the beta 1 subunit of integrin, but was completely blocked by a combination of these 2 antibodies. These antibodies markedly inhibited the dissemination of NUGC-4 cells in the peritoneal cavity of nude mice, and prolonged their mean survival time. These findings suggest that s-Le(x) and E-selectin mediate the adhesion of gastric cancer cells to endothelial cells, and CD44H and beta 1 integrin play important roles in the initial attachment of gastric cancer cells to mesothelial cells. It is possible that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of gastric cancer metastasis.

Animals↗

PubMedDate not supplied

Increased concentration of soluble E-selectin in the sera of breast cancer patients.

E-selectin which is expressed on endothelial cells plays an important role in the adhesion of cancer cells to the vascular endothelium, being the ligand for a carbohydrate antigen expressed on cancer cells. In this study, the clinical usefulness of this protein was examined. E-selectin was expressed on the endothelial cells of the small vessels adjacent to the cancer nests in 63 of the 104 (60.6%) primary tumors of breast cancer. The expression of E-selectin in locations adjacent to the cancer nests was more pronounced than that in distant ones. The mean value of serum soluble E-selectin (ng/ml) was 38.3 in benign breast disease, 47.8 in those with no evidence of recurrence, 49.4 in stage I/II primary breast cancer, 75.8 in stage III/IV primary breast cancer, and 93.7 in recurrent breast cancer. The mean value of serum soluble E-selectin was 106.2 ng/ml in patients with distant metastases, and 50.4 ng/ml in those with no evidence of distant metastases. Thus, the concentration of soluble E-selectin was significantly elevated in the sera of patients with distant metastases. These findings suggested that cancer cells induced the expression of E-selectin on endothelial cells and, that serum soluble E-selectin is useful as a tumor marker having a close relationship to metastasis in breast cancer.

Biomarkers, Tumor↗

PubMedDate not supplied

The association of sialyl Lewis(a) antigen with the metastatic potential of human colon cancer cells.

BACKGROUND: The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between a cell line derived from human colon cancer and cultured murine endothelial cells, in vitro, and in vivo. MATERIALS AND METHODS: Variant cell lines with high (WiDr-HA) or low (WiDr-LA) levels of cell surface sialyl Lewis(a) antigen (s-Le(a)) were isolated from the heterogeneous WiDr cells (WiDr-P) in order to characterize the biological behavior of colon cancer cells having elevated cell surface contents of s-Le(a). RESULTS: A correlation was found to exist between the degree of s-Le(a) expression, and the attachment of cancer cells to activated human umbilical vein endothelial cells, or to F-2 cells isolated from murine vascular endothelial cells. The adhesion of WiDr-P and WiDr-HA to F-2 cells was inhibited by the addition of anti-s-Le(a) antibody (Ab). WiDr-P and WiDr-HA both demonstrated the capacity to metastasize to the liver, by the inoculation of cancer cells to the spleen, while WiDr-LA did not do so. The number of metastatic nodules of WiDr-HA was significantly higher than that of WiDr-P. Treatment with anti-s-Le(a) Ab inhibited the metastasis of WiDr-P and WiDr-HA to the liver, but not with anti-s-Le(x) Ab. CONCLUSIONS: These findings suggest that s-Le(a) plays an important role in cell adhesion molecules, in the metastasis of colon cancer.

Animals↗

PubMedDate not supplied

Altered expression of integrins in adriamycin-resistant human breast cancer cells.

We investigated alterations in the expression of integrin on adriamycin-resistant MCF-7 (MCF-7/ADR) cells, which had been selected from MCF-7 human breast cancer cells, in order to examine the mechanisms behind the acquisition of malignancy in breast cancer progression. Expression of the alpha 6 integrin subunit of MCF-7/ADR cells was stronger than that of MCF-7 cells, whereas expression of alpha 2 integrin subunit of MCF-7/ADR cells was weaker than that of MCF-7 cells. MCF-7/ADR showed increased binding activity to laminin, but not to collagen or fibronectin, compared to those of parental MCF-7 cells. Adhesion of MCF-7 cells to collagen and laminin was inhibited by the addition of antibody to alpha 2 and alpha 6 integrin subunit, respectively. On the other hand, adhesion of MCF-7/ADR cells to collagen was not inhibited by the addition of antibody to alpha 2, alpha 3 or alpha 6 integrin subunit. Adhesion of MCF-7/ADR cells to laminin was inhibited by not only the antibody to alpha 6 subunit but also the antibody to the alpha 3 subunit. The transmigratory activity of MCF-7/ADR cells was higher than that of MCF-7 cells. A significant inhibitory effect on the transmigration of MCF-7/ADR cells was observed by the addition of antibody to alpha 6 and beta 1 integrin subunit. MCF-7/ADR cells appeared smaller and flatter than MCF-7 cells, and spread to a greater extent on the culture dish. MCF-7 cells cultured on Matrigel for 24 hours formed clusters. In contrast to this, MCF-7/ADR cells expanded with a tubular-like pattern on Matrigel. The spread of MCF-7/ADR cells was incompletely inhibited by addition of the antibody to alpha 3 integrin subunit, and completely inhibited by addition of the antibody to alpha 6 and beta 1 integrin subunit. These findings suggest that integrins on MCF-7/ADR cells are altered from those on parental MCF-7 cells in not only expression but also function, and that interaction between cancer cells and extracellular matrix protein is involved in augmentation of the invasiveness of MCF-7/ADR cells.

Breast Neoplasms↗