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Purification and Some Properties of a Lung-derived Growth Factor That Differentially Stimulates the Growth of Tumor Cells Metastatic to the Lung¹

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

The ability of malignant cells to respond to growth factor(s) present in or secreted by a distant target organ may be important in tumor metastasis. We used metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma that show reproducible spontaneous metastatic behavior from the mammary fat pad to regional lymph nodes and lung sites. Whereas poorly lung metastatic MTPa and MTC cells did not grow in response to lung-conditioned medium, highly lung-metastatic MTLn3 cells responded and grew rapidly in lung-conditioned medium. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was purified by using hydroxylapatite affinity and anion exchange chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured by determining their ability to increase the number of MTLn3 cells in serum-deprived culture. The major component that differentially stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of M_r 66,000. Under reducing conditions, its apparent M_r was 72,000. This lung-derived mitogen was stable at pH 4.0–9.0, possessed a pI of 6.9–7.0, and preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in rat 13762NF mammary adenocarcinoma and murine B16 melanoma tumor systems. The activity of porcine lung-derived growth factor was not affected by pretreatment with antisera to porcine insulin, human granulocyte-macrophage colony-stimulating factor, human platelet-derived growth factor, or murine epidermal growth factor. It was inactivated by reduction with dithiothreitol or exposure to high temperature (95°C). The results suggest that specific organ-derived growth factors are important in metastatic colonization and organ growth of particular malignant cells.

¹ This investigation was supported by Grant R35-CA44352 (OIG) awarded by the National Cancer Institute, Department of Health and Human Services (to G. L. N.).

² To whom all requests for reprints should be addressed, at the Department of Tumor Biology (Box 108), The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 11/18/88. Revised 3/29/89. Accepted 4/20/89.

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