Association of CD98, integrin ß1, integrin ß3 and Fak with the progression and liver metastases of colorectal cancer.

ABSTRACT

CD98-mediated ß1 and ß3 integrins activation can induce Fak phosphorylation which eventually promotes cell survival, proliferation, and migration. We evaluated the expression of CD98, integrin ß1, integrin ß3 and Fak in 45 cases of matched colorectal cancer (CRC) and liver metastases as well as 35 cases of CRC without liver metastases. There was a gradual increase of the expression of CD98, integrin ß1, integrin ß3 and Fak as tumor progressed from normal colon to carcinoma to budding tumor cells at the invasive front and to liver metastases. The expression of CD98 and integrin ß1 in CRC with liver metastases was significantly higher than that in CRC without liver metastases. Furthermore, for those liver metastases with desmoplastic growth pattern, expression of CD98, integrin ß1, integrin ß3 and Fak at the metastases center was as strong as that at the metastases periphery. For those liver metastases with pushing or replacement growth patterns, more intense expression of these markers was found at the metastases center than the periphery. Overexpression of CD98, integrin ß1, integrin ß3 and Fak is associated with the progression and liver metastases of CRC. Overexpression of these markers in liver metastases requires direct contact between tumor cells and the stroma.