THE LCC15-MB HUMAN BREAST-CANCER CELL-LINE EXPRESSES OSTEOPONTIN AND EXHIBITS AN INVASIVE AND METASTATIC PHENOTYPE

We have characterized the LCC15-MB cell line which was recently derive d from a breast carcinoma metastasis resected from the femur of a 29-y ear-old woman. LCC15-MB cells are vimentin (VIM) positive, exhibit a s tellate morphology in routine cell culture, and form penetrating colon ies when embedded in three-dimensional gels of Matrigel or fibrillar c ollagen. They show high levels of activity in the Boyden chamber chemo migration and chemoinvasion assays, and Like other invasive human brea st cancer (HBC) cell lines, LCC15-MB cells activate matrix-metalloprot einase-2 in response to treatment with concanavalin A. In addition, th ese cells are tumorigenic when implanted subcutaneously in nude mice a nd recolonize bone after arterial injection. Interestingly, both the p rimary lesion and the bone metastasis from which LCC15-MB were derived , as well as the resultant cell line, abundantly express the bone matr ix protein osteopontin (OPN). OPN is also expressed by the highly meta static MDA-MB-435 cells, but not other invasive or noninvasive HBC cel l lines. Expression of OPN is retained in the subcutaneous xenograft a nd intraosseous metastases of LCC15-MB as detected by immunohistochemi stry. Both VIM and OPN expression have been associated with breast can cer invasion and metastasis, and their expression by the LCC15-MB cell . line is consistent with its derivation from a highly aggressive brea st cancer. These cells provide a useful model for studying molecular m echanisms important for breast cancer metastasis to bone and, in parti cular, the implication(s) of OPN and VIM expression in this process. ( C) 1998 Academic Press.