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American Journal of Pathology, Vol 99, 43-52, Copyright © 1980 by American Society for Investigative Pathology

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Partial characterization of a bone-derived chemotactic factor for tumor cells

FW Orr, J Varani, MD Gondek, PA Ward and GR Mundy

Medium that has been bathing organ cultures of resorbing bone contains a factor that is chemotactic for cultured Walker carcinosarcoma cells, as assayed by the Boyden chamber technique. There is a positive correlation between the chemotactic activity released by the resorbing bones and the extent of resorption as measured by release of previously incorporated 45Ca from the bones. Generation of the chemotactic factor occurs independent of the humoral mediator of bone resorption. The tumor cell chemotactic factor has a steep dose-response curve, with a fall from maximal to minimal activity extending over a four-fold dilution. The chemotactic activity is stable to heating and has an estimated molecular weight of 6000 daltons, as determined by gel filtration chromatography and retention of activity following dialysis. The chemotactic activity has been distinguished from the tumor cell chemotactic factor derived from the fifth component of complement because the former is not inactivated by antiserum to C5 and because it is chemotactic for EL-4 lymphoma cells, whereas the latter is not chemotactically active for these cells.