B16 MELANOMA VARIANTS SELECTED BY ONE OR MORE CYCLES OF SPONTANEOUS METASTASIS TO THE SAME ORGAN FAIL TO EXHIBIT ORGAN SPECIFICITY

Metastatic clones of the mouse B16 melanoma spontaneously disseminate from subcutaneous tumors throughout the body in two stages, initially to the lungs and secondarily from established lung metastases to systemic sites. From the heterogeneous 'parent' B16 melanoma cell line and from two representative clones, G3.5 and G3.12, cell populations were selected after one or more cycles of tumor growth or metastasis to a particular site, to determine whether metastatic variants with greater organ preference or specificity could be generated. Variants with enhanced secondary metastatic activity were obtained only from G3.12 tumor-disseminated metastases growing in the lungs or in systemic organs. Regardless of the organ of selection or the number of selection cycles, all variants exhibited an overall increase in secondary metastasis incidence and burden in the brain, adrenals, kidneys and ovaries, but no organ preference or specificity was obtained. Populations that grew especially well in the brain, ovaries or liver following intravascular injection were either non-metastatic or exhibited no organ preference during spontaneous metastasis. The increased secondary metastatic activity of G3.12 variants was apparently not due to either longer host survival or to tumor-disseminated cells bypassing the lungs, but may result from enhanced growth potential or greater secondary dissemination capability imparted during growth as lung metastases.