This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Staroselsky, A. N. Articles by Fidler, I. J. Search for Related Content PubMed PubMed Citation Articles by Staroselsky, A. N. Articles by Fidler, I. J.

Site-dependent Differences in Response of the UV-2237 Murine Fibrosarcoma to Systemic Therapy with Adriamycin¹

Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Murine fibrosarcoma UV-2237MM cells were implanted into different organs of syngeneic C3H/HeN mice. The resultant tumors were treated by i.v. administration of Adriamycin (ADR). Despite the high sensitivity of the fibrosarcoma cells to ADR in vitro, the established tumors growing in vivo exhibited marked differences in their responses to ADR. Tumors growing in the subcutis and the spleen were ADR-sensitive, whereas lung metastases were not. The resistance of lung metastases to ADR was not due to selection of a drug-resistant population since tumor cells isolated from lung metastases were highly sensitive to ADR under in vitro conditions. The responsiveness of skin and spleen tumors to ADR was due neither to increased blood supply nor to preferential accumulation of ADR, since both parameters were higher in lung metastases. Protein kinase C activity levels correlated with ADR resistance in the closely related murine fibrosarcoma cell line UV-2237 and its ADR-selected multidrug-resistant variants. However, nearly identical levels of protein kinase C activity were found in UV-2237MM tumors growing in the lung, spleen, and subcutis, indicating that protein kinase C activity levels did not account for the different responses to ADR. The present studies suggest that the organ environment influences the response of UV-2237MM to ADR administered systemically. This finding may have implications for the design of animal models for therapy of disseminated cancer.

¹ Supported by Core Grant CA16672 and Grant R35 CA42107 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed, at the Department of Cell Biology (HMB 173), The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 4/24/90. Accepted 9/17/90.

This article has been cited by other articles:

				R. E. Mudry, J. E. Fortney, T. York, B. M. Hall, and L. F. Gibson Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy Blood, September 1, 2000; 96(5): 1926 - 1932. [Abstract] [Full Text] [PDF]