Implication of tyrosine kinase receptor and steel factor in cell density-dependent growth in cervical cancers and leukemias

Cell-cell interaction is important in the expansion of leukemic cells and o f solid tumors. Steel factor (SF) or Kit ligand is produced as a membrane-b ound form (mSF) and a soluble form. Because both primary gynecological tumo rs and primary leukemic cells from patients with acute myeloblastic leukemi a (AML) have been shown to coexpress c-Kit and SF, we addressed the questio n of whether mSF could contribute to cell interaction in these cancers. Inv estigations on primary cervical carcinomas have been hindered by the fact t hat the cells do not grow in culture. We report herein the establishment of two cervical carcinoma cell lines, CALO and INBL, that reproduce the patte rn of SF/c-Kit expression observed in primary tumor samples. In addition, t hese cells exhibit marked density-dependent growth much in the same way as AML blasts. Using an antisense strategy with phosphorothioate-modified olig onucleotides that specifically target SF without affecting other surface ma rkers, we provide direct evidence for a role of mSF and c-Kit in cell inter action and cell survival in these gynecological tumor cell lines as well as in primary AML blasts. Finally, our study defines the importance of juxtac rine stimulation, which may be as important, if not more, than autocrine st imulation in cancers.