THE ESTABLISHMENT OF 2 CELL-LINES FROM A MOUSE UTERINE CERVICAL-CARCINOMA (U-14) AND THEIR METASTATIC PHENOTYPE CHANGES

This paper studies the heterogeneity of metastatic potential of murine cervical carcinoma (U-14). TWO fell lines, P-11-90 and L(10-90), were established from a pulmonary metastatic substrain (U(14)AP(11)) and a lymphatic metastatic substrain (U(14)AL(10)), Which were selected fro m U-14 in vivo after 11 and 10 passages, respectively. The biologic di fferences between the two cell lines are as follows. (1) The cells of the P-11-90 line grow more rapidly compared with the L(10-90) line. Fr om the 40th passage the medium pH was different. (2) The median number of chromosomes in P-11-90 and L(10-90) was 72 and 64, respectively; t he rates of gap aberration were 88% and 78%, respectively. (3) The num ber of T lymphocytes and T helper lymphocytes in the peripheral blood from hosts with P-11-90 were higher than that of hosts transplanted wi th L(10-90), but the number of B lymphocytes in the latter was larger than that in the former. (4) The metastatic potential of each cell lin e partially decreased compared to the relative tumor substrain, but th eir organ preference still remained and the transplant locations, axil lary or footpad, had a prominent influence on their metastatic behavio r. To observe the effects of metastatic target organs on the metastati c phenotypes of tumor cells, as well as to explore a method for the es tablishment and maintenance of the metastatic organ preference of tumo r cells, conditioned medium (CM) from pulmonary or lymphatic node dipl oid cells was added to the culture medium of P-11-90 and L(10-90). Two sublines, P+P-11-90 and Ln+L(10-90), were thus established. Using ste reological methods we found that the majority of P+P-11-90 cells becam e larger and their nuclei also increased in size compared with their p arental lines, but the majority of Ln+L(10-90) cells became smaller in size, though the nuclei were enlarged. The pulmonary metastatic rate and lymphatic metastatic rate of P + P-11-90, as well as the lymphatic metastatic rate of Ln + L(10-90), were restored dramatically. The res ults suggest that by taking advantage of the interaction between tumor cells and the CM of host cells the metastatic potential of tumor cell lines can be maintained in vitro. Our work may offer an experimental model for the manipulation of metastasis of cell lines coming from the same parent strain but with different metastatic potentials. Our stud y demonstrates that although the specific metastatic tendencies of the cell lines decrease after multiple passages, these propensities are r estored after passages with CM from normal lung and lymph node tissue.