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.
Narita
T
T
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Kimura
N
N
Sato
M
M
Matsuura
N
N
Kannagi
R
R
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen; D004317:Doxorubicin; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007797:Laminin; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D004338:Drug Combinations; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D004317:Doxorubicin; D003094:Collagen