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6 Integrin Is Up-regulated in Step Increments Accompanying Neoplastic Transformation and Tumorigenic Conversion of Human Fibroblasts¹

Laboratory of Cancer Cell Biology, Palo Alto Medical Foundation Research Institute, Palo Alto, California 94301 [C-S. L.], and Department of Stomatology and Anatomy, University of California, San Francisco, California 94143 [C-S. L., K. Z., R. K.]

Integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular differentiation and proliferation. In malignant cells, which exhibit abnormal differentiation and growth properties, the expression of an altered integrin repertoire could therefore be expected. From a tumorigenic human fibrosarcoma cell line we isolated a unique complementary DNA corresponding to the 6 integrin subunit. Northern blot analysis using this complementary DNA as probe indicated that 6 integrin mRNA was abundantly expressed in all neoplastically transformed fibroblast cell lines but not in normal diploid fibroblasts. In addition to its potential as a marker for the neoplastic transformation of human fibroblasts, the 6 integrin mRNA was also found to be consistently expressed at higher levels in tumorigenic fibroblasts than in immortalized but nontumorigenic fibroblasts. This differential expression of 6 integrin was reflected at the cell surface protein level using cytofluorometric analysis with specific monoclonal antibody. In contrast, the levels of cell surface expression of other integrins were unchanged (such as 3 and ß1) or down-regulated (such as 5) when transformed cells were compared with normal fibroblasts. The incremental up-regulation of 6 integrin was selective and paralleled the progression of normal cells to immortalized cells and finally to tumorigenic cells. This elevated 6 subunit associated with the ß1 subunit to form a heterodimer receptor for laminin. Since fibrosarcoma cell invasion of basement membrane has been shown to involve 6ß1 integrin, then the induction or up-regulation of 6 expression is an important step in tumor progression and evolution to the invasive phenotype in fibrosarcoma.

¹ Supported by NIH Grants CA49423 (C-S. L.), CA51884, DE10564 (R. K.), and Chapman Research Fund (C-S. L.).

² To whom requests for reprints should be addressed.

Received 3/31/93. Accepted 5/18/93.

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