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In most studies concerning organ-specific metastasis, different or selected lines are compared with one another. Here we report results with the same cell line (the F9 murine teratocarcinoma) which can be directed towards liver or lung, depending on whether or not it is treated with retinoic acid and cyclic AMP. Thus, organ-specific colonization by tail-vein-injected murine F9 teratocarcinoma cells shows a particular pattern: unselected, undifferentiated F9 cells preferentially colonize the liver of the syngeneic animal. The lungs, the first capillary bed encountered by cells thus injected, are only very rarely colonized. By contrast, the lungs become the main target organ of F9 cells induced to differentiate by treatment with retinoic acid and cyclic AMP. We have recently shown that liver colonization by undifferentiated F9 cells correlated with the adhesiveness of the cells (higher to fibronectin and liver-derived extracellular matrix than to laminin and lung-derived extracellular matrix) as well as with their growth response to organ-derived extracts (no response with lung extracts and good response with liver extracts). The data reported below indicate that induction of differentiation causes at most a decreased adhesiveness of F9 cells to all the substrata tested (laminin, fibronectin, type-IV collagen, organ-derived extracellular matrix), suggesting that the shift in organ colonization observed with differentiated F9 cells is not due to an enhancement of the specific adhesion to the lung matrix. On the other hand, differentiated cells, but not undifferentiated ones, were able to respond to growth stimulation mediated by lung-derived extracts, thereby implying a relevant role for organ-specific growth stimulation in lung colonization by differentiated F9 cells. © 1992 Wiley-Liss, Inc.

Unselected F9 murine embryonal carcinoma cells preferentially colonize the liver upon injection into tail veins of syngeneic mice, while the lungs are only very rarely colonized. Here we show that F9 cells attach better to fibronectin than to laminin in an adhesion assay, like other liver-colonizing cell lines. Moreover, assays of adhesion to extracellular matrix (ECM) prepared from rat organs (liver, lung and kidney) demonstrate that, in the absence of serum, F9 cells adhere better to liver- than to kidney- or lung-derived ECM. Even in the presence of FCS, the adhesion to lung ECM remains very low. This very low adhesiveness of F9 cells to lung-derived ECM correlates well with the finding that, in an organ distribution assay, tail-vein-injected F9 cells are very rapidly released from the lungs, when compared to the retention times of the lung-specific murine melanoma cell line B16-F10. Yet another property appears to contribute to organ-specific colonization of these cells: extracts of liver promote the growth of F9 cells, in contrast to extracts of lung or kidney which have no effect. These data suggest that preferential formation of metastases in the liver following the intravenous injection of F9 cells is the result of both their adhesive abilities and their growth response to local microenvironment.