Melanoma growth and tumorigenicity in models of microgravity.
BACKGROUND
Spaceflight involves numerous biological stressors that could affect long-term cancer incidence and tumor behavior. Ground-based models of microgravity can be used to investigate in vitro and in vivo tumor growth as a preparation for later work in space. The incidence of tumor growth and carcinogenesis in microgravity is as yet unknown. Hence, we investigated the effects of modeled microgravity on tumor growth and tumorigenicity using ground-based in vitro and in vivo models.


METHODS
Murine B16-F10 melanoma cells were cultured in a tissue culture flask (FL) and in a rotating-wall vessel bioreactor (BIO) designed by NASA to simulate some aspects of microgravity. We then measured cell growth, melanin production, and apoptosis. After 48 h of cultures in FL and BIO, cells were inoculated subcutaneously in C57BL/6 mice, syngeneic hosts for B16-F10 tumor cells. Tumor sizes were then measured every other day.


RESULTS
BIO cultures had 50% decreases in growth when compared with FL cultures while demonstrating an inversely proportional increase in doubling time. Melanin production (a marker of differentiation) increased at 24 and 48 h in BIO. Flow cytometry analysis demonstrated that there was an increase in the percentage of apoptotic cells in the BIO when compared with that in the FL. When BIO-cultured melanoma cells were inoculated subcutaneously in mice, there was a significant increase in tumorigenicity as compared with FL-cultured cells.


CONCLUSIONS
Our results indicate that simulated microgravity may have altered the tumor cell characteristics and enhanced the invasive property. It is possible that the microgravity analogue culture environment may have selected highly tumorigenic cells for survival despite the decreased overall growth in the microgravity analogue.
Taga
Masaki
M
Department of Applied Clinical Nutrition, Kitasato Junior College of Health and Sciences, Yamato Niigata, Japan, USA.
Yamauchi
Keiko
K
Odle
Jesse
J
Furian
Lucrezia
L
Sundaresan
Alamelu
A
Ramesh
Govindrajan T
GT
Pellis
Neal R
NR
Andrassy
Richard J
RJ
Kulkarni
Anil D
AD
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D008543:Melanins / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D018474:Weightlessness Simulation
D008543:Melanins