Characterization of the role of Samsn1 loss in multiple myeloma development.

Autor: Friend NL; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Hewett DR; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Panagopoulos V; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Noll JE; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Vandyke K; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Mrozik KM; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Fitter S; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia., Zannettino ACW; Myeloma Research Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide Australia.; Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide Australia.; Central Adelaide Local Health Network Adelaide Australia.
Jazyk: angličtina
Zdroj: FASEB bioAdvances [FASEB Bioadv] 2020 Aug 05; Vol. 2 (9), pp. 554-572. Date of Electronic Publication: 2020 Aug 05 (Print Publication: 2020).
DOI: 10.1096/fba.2020-00027
Abstrakt: The protein SAMSN1 was recently identified as a putative tumor suppressor in multiple myeloma, with re-expression of Samsn1 in the 5TGM1/KaLwRij murine model of myeloma leading to a near complete abrogation of intramedullary tumor growth. Here, we sought to clarify the mechanism underlying this finding. Intratibial administration of 5TGM1 myeloma cells into KaLwRij mice revealed that Samsn1 had no effect on primary tumor growth, but that its expression significantly inhibited the metastasis of these primary tumors. Notably, neither in vitro nor in vivo migration was affected by Samsn1 expression. Both knocking-out SAMSN1 in the RPMI-8226 and JJN3 human myeloma cell lines, and retrovirally expressing SAMSN1 in the LP-1 and OPM2 human myeloma cell lines had no effect on either cell proliferation or migration in vitro. Altering SAMSN1 expression in these human myeloma cells did not affect the capacity of the cells to establish either primary or metastatic intramedullary tumors when administered intratibially into immune deficient NSG mice. Unexpectedly, the tumor suppressive and anti-metastatic activity of Samsn1 in 5TGM1 cells were not evidenced following cell administration either intratibially or intravenously to NSG mice. Crucially, the growth of Samsn1-expressing 5TGM1 cells was limited in C57BL/6/Samsn1 -/- mice but not in C57BL/6 Samsn1 +/+ mice. We conclude that the reported potent in vivo tumor suppressor activity of Samsn1 can be attributed, in large part, to graft-rejection from Samsn1 -/- recipient mice. This has broad implications for the design and interpretation of experiments that utilize cancer cells and knockout mice that are mismatched for expression of specific proteins.
Competing Interests: The authors declare no conflicts of interest.
(© 2020 The Authors. FASEB BioAdvances published by the Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
Externí odkaz: