TY - JOUR
T1 - Modifying Effects of Glucose and Insulin/Insulin-Like Growth Factors on Colon Cancer Cells
AU - Berk, Şeyda
AU - Janssen, Joseph A.M.J.L.
AU - van Koetsveld, Peter M.
AU - Dogan, Fadime
AU - Değerli, Naci
AU - Özcan, Servet
AU - Kelestimur, Fahrettin
AU - Hofland, Leo J.
N1 - Publisher Copyright:
© Copyright © 2021 Berk, Janssen, van Koetsveld, Dogan, Değerli, Özcan, Kelestimur and Hofland.
PY - 2021/7/5
Y1 - 2021/7/5
N2 - There are only a few experimental studies which have investigated effects of glucose alone, and glucose in combination with insulin/insulin-like growth factors (IGF) on the growth of colon cancer. In the present study, we studied in vitro in human colorectal cancer cells originating from four Dukes’ stages of colorectal cancer the effects of glucose, insulin and IGFs on proliferation, migration, cell cycle progression and gene expression of the IGF system. Growth of colon cancer cells originating from a Dukes’ stage A was glucose-dependent, whereas growth of cancer cells from Dukes’ stage B, C and D was glucose-independent. Stimulatory effects of insulin and IGFs on cell growth were observed only in colon cancer cells originating from Dukes’ stage C and D. IGF-II stimulated migration in Dukes’ stage B cells only. The growth stimulatory effects in Dukes’ stage C and D colorectal cancer cells were accompanied by G2/M arrest and associated with an increased IGF-IR/IGF-II receptor ratio. In conclusion, our in vitro data suggest that the stimulating effects of glucose, IGFs and insulin on proliferation differ between colorectal cancer cells from early and late Dukes’ stages. Stimulatory effects of glucose on proliferation appear predominantly present in stage Dukes’ stage A colorectal cancer cells, while in contrast growth factor-mediated stimulation of cell proliferation is more pronounced in Dukes’ late stage (metastasized) colorectal cancer cells. Moreover, our study suggests that a stringent glucose control may be important to control tumor growth in early stages of colorectal cancer, while inhibition of the endocrine actions of the IGFs and insulin become more important in the late (metastasized) stages of colorectal cancer to restrain growth of colon cancer cells.
AB - There are only a few experimental studies which have investigated effects of glucose alone, and glucose in combination with insulin/insulin-like growth factors (IGF) on the growth of colon cancer. In the present study, we studied in vitro in human colorectal cancer cells originating from four Dukes’ stages of colorectal cancer the effects of glucose, insulin and IGFs on proliferation, migration, cell cycle progression and gene expression of the IGF system. Growth of colon cancer cells originating from a Dukes’ stage A was glucose-dependent, whereas growth of cancer cells from Dukes’ stage B, C and D was glucose-independent. Stimulatory effects of insulin and IGFs on cell growth were observed only in colon cancer cells originating from Dukes’ stage C and D. IGF-II stimulated migration in Dukes’ stage B cells only. The growth stimulatory effects in Dukes’ stage C and D colorectal cancer cells were accompanied by G2/M arrest and associated with an increased IGF-IR/IGF-II receptor ratio. In conclusion, our in vitro data suggest that the stimulating effects of glucose, IGFs and insulin on proliferation differ between colorectal cancer cells from early and late Dukes’ stages. Stimulatory effects of glucose on proliferation appear predominantly present in stage Dukes’ stage A colorectal cancer cells, while in contrast growth factor-mediated stimulation of cell proliferation is more pronounced in Dukes’ late stage (metastasized) colorectal cancer cells. Moreover, our study suggests that a stringent glucose control may be important to control tumor growth in early stages of colorectal cancer, while inhibition of the endocrine actions of the IGFs and insulin become more important in the late (metastasized) stages of colorectal cancer to restrain growth of colon cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=85110598246&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.645732
DO - 10.3389/fonc.2021.645732
M3 - Article
AN - SCOPUS:85110598246
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 645732
ER -