Effect of Polymorphonuclear Cells on Invasive and Metastatic Potentials of 13762NF Rat Mammary Adenocarcinoma Cells
Schissel, Daniel John
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The number of circulating activated polymorphonuclear leukocytes (PMNs) increases in tumor-bearing rats in a manner corresponding to the metastatic propensity of the tumor cell inoculated. Because secretion of basement membrane degrading proteinases was also enhanced, it was proposed that activated PMNs may play a role in tumor metastasis, particularly tumor cell extravasation. To test this hypothesis, we measured the effects of normal PMNs and circulating PMNs isolated from peripheral blood of tumor bearing rats on the experimental metastatic and invasive potentials of 13762NF rat mammary adenocarcinoma cell clones. Circulating PMNs isolated from MTLn3 tumor-bearing rats increased the invasion potentials of 13762NF rat mammary adenocarcinoma clones in vitro when tested in the Membrane Invasion Culture System (MICS) using reconstituted basement membrane as a barrier, and experimental metastatic potentials in vivo in a dose dependent manner. In contrast, 'normal' PMNs isolated from peripheral blood, or proteose peptone-stimulated peritoneal exudate did not alter these malignant characteristics. When rats received intravenous co-injections of tumor-elicited PMNs and tumor cells at an effector:target (E:T) ratio of 50:1 the mean number of experimental lung metastases rose 23. 2-fold for weakly metastatic MTLn2, 1.6-fold for moderately metastatic, highly invasive MTF7 clone, and 3.0-fold for the highly metastatic MTLn3 clone. In vitro invasive potentials were measured in MICS with varying E:T ratios (up to 30:1) of tumor-elicited PMNs and tumor cells. Invasive potential increased up to 25.5-fold for MTLn2, 36.7-fold for MTF7, and 53.7-fold for MTLn3. These results indicate that PMNs isolated from MTLn3 tumor-bearing rats have properties that can contribute to the metastatic potentials of other 13762NF rat mammary adenocarcinoma clones by assisting their invasion through a reconstituted basement membrane.