engleski

The role of coxsackievirus and adenovirus receptor in cell sensitivity to anticancer drugs

The role of coxsackievirus and adenovirus receptor (CAR) has been intensively explored and elucidated in adenovirus infection, while its role in normal cell physiology remains unclear. CAR functions as a transmembrane component of epithelial tight junctions and adherens junctions. In tumor cells CAR expression is reduced or absent while its overexpression inhibits cell proliferation, migration and metastasis, implying that CAR is a tumor-suppressor molecule. Adhesion molecules may have a role in cell sensitivity to anticancer drugs. Therefore we explored the role of CAR in cell response to anticancer drugs. Rhabdomyosarcoma (RD) tumor cell line that physiologically expresses very little CAR was used as the model system. CAR expressing clones A7, G7 and D6 were established from RD cells by stable transfection. Using spectrophotometric MTT assay we examined their sensitivity to different cytostatics and compared it with that of RD cells. The overexpression of CAR in RD cells did not change sensitivity to cisplatin. However, the sensitivity to other anticancer drugs was altered for G7 and D6 clones, but not for A7 clone, which has the lowest level of CAR expression. Cell clones G7 and D6 were found to be resistant to vincristine, but sensitive to mitomycin C and doxorubicine. To examine whether the involvement of CAR in cell sensitivity to different anticancer drugs is a general phenomenon, CAR silencing experiments using cells expressing high constitutive level of CAR are under way. Our results suggest a new, formerly unknown, function of CAR in cell response to anticancer drugs.

Coxsackievirus and adenovirus receptor (CAR); cell sensitivity; anti-cancer drugs

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