SC1, an immunoglobulin-superfamily cell adhesion molecule, is involved in the brain metastatic activity of lung cancer cells

Abstract

Abstract. SC1 is a cell adhesion molecule that belongs to the immunoglobulin superfamily; this molecule was initially purified from the chick embryonic nervous system and was reported to exhibit homophilic adhesion activity. SC1 is transiently expressed in various organs during development and has been identified in numerous neoplastic tissues, including lung cancer and colorectal carcinomas. The present study focused on the encephalic metastasis of lung cancer cells with respect to the potential function of SC1, as this molecule is known to be consistently expressed in the central nervous system as well as lung cancers. SC1 complementary DNA was introduced into A549 cells, a human lung cancer-derived cell line. The stable overexpression of the SC1 protein in A549 cells was demonstrated to enhance the self-aggregation of the cells. In addition, the SC1 transfectants enhanced the metastatic and invasive potential to the encephalic parenchyma following implantation into nude mice. In conclusion, the results of the present study demonstrated that cell adhesion due interactions between SC1 on brain tissue and SC1 on lung cancer cells was involved in the malignant aspects of lung cancer, including invasion and metastasis to the brain. IntroductionNumerous studies have confirmed that cell adhesion molecules (CAMs) are essential for normal histogenesis as well as tumor malignancies (1-3). In addition, it was reported that dysregulated CAM expression was often involved in certain tumor behavior (4,5). Of note, the inhibition or attenuation of E-cadherin expression in epithelial cells was demonstrated to enhance cellular transformation. A certain CAM, deleted in colorectal cancer (DCC), is a member of the immunoglobulin (Ig) superfamily, which is commonly lost during the development of colorectal tumors. The loss of expression of CAMs, such as DCC, has therefore been suggested to enable the migration and escape of tumor cells from the primary lesion, subsequently resulting in the invasion and the dissemination of metastases. By contrast, various other CAMs have been reported to be overexpressed in numerous types of tumors, which may promote tumor cell invasion and metastasis through their adhesive activities (4,6).SC1 is a cell adhesion molecule that belongs to the Ig superfamily; this molecule was identified in several independent studies, each of which gave it a different title, SC1, bursal epithelium and neurons or DM-general receptor for phosphoinositides 1-associated scaffold protein (7-10). This protein possesses an intracellular domain that carries three C2-type Ig-like motifs followed by two V-type motifs. The homophilic properties of SC1 have been revealed using cellular adhesion experiments on substrates and self-aggregation assays in vitro (8,(11)(12)(13). By contrast, previous studies have also reported heterophilic interactions of SC1, such as that with neuron-glia (Ng)-CAM during the extension of neurites from sympathetic neurons as well as that with CD6 in the hematopoietic system (14,15). SC1 homologs hav...

Experimental Therapeutic Trial of an Antibody against the Cell Adhesion Molecule Gicerin for Lymphomas Using a Murine Cell Line

“…Gicerin is almost entirely absent in mature tissues, being restricted to muscles and endothelial cells in blood vessels. However, gicerin has been found to be over expressed in various sporadic tumors in animals [11] [14]- [19] [22] [23] [24]. It has also been demonstrated that lymphoma cells strongly express gicerin in their membrane.…”