Denning 2013

KISS1-expressing tumor cells interact with myeloid lineage cells that promote/allow growth at orthotopic sites but another subset prevents outgrowth/colonization at ectopic sites

Warren Denning and Danny Welch

Re-expression of the metastasis suppressor KISS1 in multiple tumor types results in significantly reduced colonization at secondary sites without inhibiting primary tumor growth, qualities which define it as a bona fide metastasis suppressor. Interestingly, expression of the KISS1 receptor (KISS1R) is not found on the metastasis suppressed tumor cell lines in which KISS1 had been re-expressed, suggesting that a paracrine signaling loop exists. A major KISS1R-expressing cell in the lung micro-environment was found to be the alveolar macrophage. Macrophages (F4/80+, CD11b+, Ly6g-) express a higher proportion of KISS1R than other myeloid cells; KISS1R positive cells display a predominantly macrophage phenotype; and co-culture with KISS1-expressing cells results in inhibition of tumor cell growth, consistent with previously published observations that KISS1 expression results in dormancy of seeded cells in the lung micro-environment. Experiments are underway to characterize the myeloid lineage cells and polarization state (i.e., M1 vs M2) in the lung versus other tissues. The working hypothesis is that KISS1-expressing tumor cells interact with myeloid lineage cells that promote/allow growth at orthotopic sites but another subset prevents outgrowth/colonization at ectopic sites. Support: CA134981, Komen SAC110037, National Foundation for Cancer Research.