Epidemiological studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. HDL is inversely associated with the risk and mortality of breast cancer. Our study is to determine the different effects of normal and diabetic HDL on breast cancer cell metastasis.

MDA-MB-231 and MCF7 cells were treated with N-HDL, D-HDL, G-HDL and Ox-HDL. Cell metastasis potency was examined using a tail-vein injection model and cell adhesion abilities to HUVEC and ECM were determined in vitro. Integrins expression and PKC activity were evaluated, and PKC inhibitor was applied.

D-HDL dramatically promoted cell pulmonary metastasis (103.6% increase at P<0.001 for MDA-MB-231 with 1x105 cell injection; 157.1% increase at P<0.05 for MCF7 with 4x105 cell injection) and hepatic metastasis (18.1-fold increase at P<0.001 for MCF7 with 4x105 cell injection), and stimulated higher TC-HUVEC adhesion (21.9% increase at P<0.001 for MDA-MB-231; 23.6% increase at P<0.05 for MCF7) and TC-ECM attachment (59.9% and 47.9% increase respectively for MDA-MB-231 and MCF7, both at P<0.01) compared with N-HDL. D-HDL stimulated higher integrins (β1, β2, β3, αν) expression on cell surface and induced higher PKC activity. Increased TC-HUVEC and TC-ECM adhesion induced by D-HDL, G-HDL and Ox-HDL could be inhibited by staurosporine.

Our study demonstrated that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on breast cancer cell adhesion to HUVEC and ECM, thereby promoting metastasis progression of breast cancer. This will largely draw the attention of HDL-based treatments in the diabetes patients with breast cancer.

PMID: 22261802 [PubMed - as supplied by publisher] Source: National Library of Medicine.