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Recombinant Human Stem Cell Factor Mediates Chemotaxis of Small-Cell Lung Cancer Cell Lines Aberrantly Expressing the c-kit Protooncogene¹

Laboratories of Immunology [Y. S., T. T., To. T.] and Chemotherapy [Ta. T., R. U., H. S., K. N.], Aichi Cancer Center Research Institute, Nagoya 464, Japan; Department of Internal Medicine, Aichi Cancer Center Hospital [T. H.], Nagoya 464, Japan; Departments of Internal Medicine I [Y. S., K. S.] and Pathology II [M. T.], Nagoya University School of Medicine, Nagoya 466, Japan; and Amgen, Inc. [K. M. Z.], Amgen Center, Thousand Oaks, California 91320

Accumulating evidence suggests that c-kit and its ligand, stem cell factor (SCF), play an important role in the regulation of at least three lineages of stem cell growth and possibly in leukemogenesis, while only limited data are available that suggest possible involvement of c-kit/SCF in the development of human solid tumors such as lung cancer. We have recently reported that c-kit is aberrantly expressed almost exclusively in small-cell lung cancer (SCLC) among various types of solid tumors. The present study revealed that c-kit protein ectopically expressed in SCLC is indistinguishable from that in leukemia cell lines with megakaryocy tic characteristics with respect to amount, molecular size, and autophosphorylation status in response to recombinant human SCF. Furthermore, significant chemotactic response as well as moderate in vitro cell growth was induced in SCLC cell lines by the addition of recombinant human SCF, suggesting that c-kit/SCF may play an important biological role in the development of SCLC. Our extensive search for activating mutations naturally occurring in the c-kit gene revealed an amino acid substitution in the transmembrane domain of an SCLC cell line, although the functional consequences of this variant allele are yet to be determined.

¹ This work was supported in part by a Grant-in-Aid for the Comprehensive Ten-Year Strategy for Cancer Research from the Ministry of Health and Welfare, Japan; Grant-in-Aids for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare, Japan; and by a grant from the Cancer Research Institute, Inc., New York.

² To whom requests for reprints should be addressed, at Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464, Japan.

Received 10/ 5/92. Accepted 1/27/93.

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