Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors

0472126 - ÚMG 2017 RIV GR eng J - Článek v odborném periodiku
Fišerová, A. - Richter, J. - Čapková, K. - Bieblová, Jana - Mikyšková, Romana - Reiniš, Milan - Indrová, Marie
Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors.
International Journal of Oncology. Roč. 49, č. 2 (2016), s. 763-772. ISSN 1019-6439. E-ISSN 1791-2423
Grant CEP: GA ČR(CZ) GA14-10100S; GA MŠMT(CZ) LM2011032; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:68378050
Klíčová slova: novel mouse strains * NKC domain * TC-1/A9 * B16F10 * MCB8 * colorectal cancer * cancer development
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.079, rok: 2016

To elucidate the immunological mechanisms critical for tumor progression, we bred novel mouse strains, different in the NKC and H-2D domains. We used inbreeding to generate hybrids of Balb/c and C57BL/6 of stable H-2Db+d-NK1.1neg and H-2Db-d+NK1.1high phenotypes. We analyzed the growth of three established MHC class I-deficient tumor cell lines: TC-1/A9 tumor (HPV-associated) and B16F10 melanoma, both syngeneic to C57BL/6, and the MCB8 (3-methycholanthreneinduced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer. We found that the novel strains spontaneously regressed the tumor transplants syngeneic to both Balb/c (MCB8) and C57BL/6 (B16F10 and TC-1/A9) mice. The H2-Db+d-NK1.1neg, but not the H2-Db-d+NK1.1high strain was also highly resistant to chemically-induced colorectal cancer in comparison to the parental mice. The immune changes during TC-1/A9 cancer development involved an increase of the NK cell distribution in the peripheral blood and spleen along with higher expression of NKG2D activation antigen; this was in correlation with the time-dependent rise of cytotoxic activity in comparison to C57BL/6 mice. The TC-1/A9 cancer regression was accompanied by higher proportion of B cells in the spleen and B220(+)/CD86(+) activated antigen-presenting B cells distributed in the lymphoid organs, as well as in the periphery. The changes in the T-cell population were represented mainly by the prevalence of T helper cells reflected by grown CD4/CD8 ratio, most prominent in the b+d-NK1.1neg strain. The results of the present study imply usefulness of the two novel mouse strains as an experimental model for further studies of tumor resistance mechanisms.
Trvalý link: http://hdl.handle.net/11104/0269474