Studies on the proteins involved in the interaction of high&amp;#x2010;density lipoprotein with isolated human small intestine epithelial cells

Dd, Sviridov; Ehnholm, Christian; Tenkanen, H; MYu, Pavlov; Ig, Safonova; Repin, V. S.

doi:10.1016/0014-5793(92)80519-m

Cited by 6 publications

(1 citation statement)

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“…In another study, AIBP promoted APOA-I binding to ATP-binding cassette transporter member 1 (ABCA1) on the cell membranes of macrophages to enhance cholesterol efflux, prevented lipid accumulation and reduced foam cell formation [15]. Early studies reported that treating enterocytes with a polyclonal antibody against AIBP inhibited [ 125 I] HDL degradation and binding to cholesterol-loaded cells, suggesting that the synergy of AIBP and APOA-I/HDL in regulating cholesterol metabolism may be a universal phenomenon in mammalian cells [16]. Therefore, we hypothesized that this synergy affects intestinal epithelial tumor development and cancer cells’ biological behavior.…”

Section: Introductionmentioning

confidence: 99%

AIBP and APOA-I synergistically inhibit intestinal tumor growth and metastasis by promoting cholesterol efflux

Zhang

Wang

et al. 2019

J Transl Med

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Background The roles played by cholesterol in cancer development and progression represent a popular field in the cancer community. High cholesterol levels are positively correlated with the risk of various types of cancer. APOA-I binding protein (AIBP) promotes the reverse cholesterol transport pathway (RCT) in cooperation with Apolipoprotein A-I (APOA-I) or high-density lipoprotein cholesterol. However, the combined effect of AIBP and APOA-I on intestinal tumor cells is still unclear. Methods Immunohistochemistry, western blot and qPCR were performed to investigate the expression of AIBP and APOA-I in intestinal tumor tissues and cell lines. The anti-tumor activity of AIBP and APOA-I was evaluated by overexpression or recombinant protein treatment. Cholesterol efflux and localization of lipid raft-related proteins were analyzed by a cholesterol efflux assay and lipid raft fraction assay, respectively. Results Here, we reported that both AIBP expression and APOA-I expression were associated with the degree of malignancy in intestinal tumors. Co-overexpression of AIBP and APOA-I more potently inhibited colon cancer cell-mediated tumor growth and metastasis compared to overexpression of each protein individually. Additionally, the recombinant fusion proteins of AIBP and APOA-I exhibited a significant therapeutic effect on tumor growth in Apc min/+ mice as an inherited intestinal tumor model. The synergistic effect of the two proteins inhibited colon cancer cell migration, invasion and tumor-induced angiogenesis by promoting cholesterol efflux, reducing the membrane raft content, and eventually disrupting the proper localization of migration- and invasion-related proteins on the membrane raft. Moreover, cyclosporine A, a cholesterol efflux inhibitor, rescued the inhibitory effect induced by the combination of AIBP and APOA-I. Conclusions These results indicate that the combination of APOA-I and AIBP has an obvious anticancer effect on colorectal cancer by promoting cholesterol efflux. Electronic supplementary material The online version of this article (10.1186/s12967-019-1910-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%