A SECOND ROUND FOR CONCOMITANT RESISTANCE IN HUMAN CANCER: A RESTRAINT UPON METASTASIS.

GERALDINE GUERON; NICOLÁS ANSELMINO; MANCHUCA DAMIAN; ORTIZ EMILIANO GERMAN; CARABELOS MARIA NOELIA; SCHUSTER FEDERICO; CHIARELLA PAULA; PAEZ ALEJANDRA; FELIPE JAWORSKI; COTIGNOLA JAVIER; MEISS ROBERTO; RUGGIERO RAUL; VAZQUEZ ELBA

Philadelphia

Congreso; American Association for Cancer Research (AACR) annual meeting 2015; 2015

AACR

Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhibits the growth of secondary tumor implants. Ehrlich first described it in 1906, but this phenomenon remained forgotten for about 60 years. After its renascence, some groups have demonstrated that both immunogenic and non-immunogenic tumors can induce CR in different animal models. Metastases could be considered as secondary tumor implants developed spontaneously during the primary tumor growth, thus CR could be relevant for cancer progression. Clinical and experimental evidence suggest that the removal of human and murine tumors might be followed by an abrupt increase in metastatic growth, hence the primary tumor could exert a controlling action on its metastases. In previous papers we demonstrated that, in mice, two temporally separate peaks of CR can be detected during murine T-lymphoma (LB) primary tumor growth. The second peak of CR is mediated by most large-sized immunogenic and non-immunogenic tumors and is associated with the anti-tumor and anti-metastatic serum factor meta-tyrosine (m-tyr), an isomer of tyrosine not present in normal proteins. Based on this background, in this work we assessed whether CR was also occurring in human tumor experimental models. Athymic nude mice were inoculated s.c. in the right flank, with the human prostate cancer cell line PC3 (1 x 106, primary implant). After 14 days the animals received a second inoculation of PC3 cells in the left flank (1 x 106, secondary implant). The control group only received the secondary implant. The growth of the secondary implant was significantly reduced (92%; P