PURPOSE: Epidemiologic studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. High-density lipoprotein (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. EXPERIMENTAL DESIGN: 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 human umbilical vein endothelial cells (HUVEC) and extracellular matrix (ECM) were determined in vitro. Integrin expression and protein kinase C (PKC) activity were evaluated, and PKC inhibitor was applied. RESULTS: D-HDL dramatically promoted cell pulmonary metastasis (103.6% increase at P < 0.001 for MDA-MB-231 with 1 × 10(5) cell injection; 157.1% increase at P < 0.05 for MCF7 with 4 × 10(5) cell injection) and hepatic metastasis (18.1-fold increase at P < 0.001 for MCF7 with 4 × 10(5) cell injection), and stimulated higher TC-HUVECs 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 integrin (β1, β2, β3, and αν) expression on cell surface and induced higher PKC activity. Increased TC-HUVECs and TC-ECM adhesion induced by D-HDL, G-HDL, and Ox-HDL could be inhibited by staurosporine. CONCLUSIONS: Our study showed that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on breast cancer cell adhesion to HUVECs 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.
PURPOSE: Epidemiologic studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. High-density lipoprotein (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. EXPERIMENTAL DESIGN: 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 human umbilical vein endothelial cells (HUVEC) and extracellular matrix (ECM) were determined in vitro. Integrin expression and protein kinase C (PKC) activity were evaluated, and PKC inhibitor was applied. RESULTS: D-HDL dramatically promoted cell pulmonary metastasis (103.6% increase at P < 0.001 for MDA-MB-231 with 1 × 10(5) cell injection; 157.1% increase at P < 0.05 for MCF7 with 4 × 10(5) cell injection) and hepatic metastasis (18.1-fold increase at P < 0.001 for MCF7 with 4 × 10(5) cell injection), and stimulated higher TC-HUVECs 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 integrin (β1, β2, β3, and αν) expression on cell surface and induced higher PKC activity. Increased TC-HUVECs and TC-ECM adhesion induced by D-HDL, G-HDL, and Ox-HDL could be inhibited by staurosporine. CONCLUSIONS: Our study showed that glycation and oxidation of HDL in diabeticpatients could lead to abnormal actions on breast cancer cell adhesion to HUVECs and ECM, thereby promoting metastasis progression of breast cancer. This will largely draw the attention of HDL-based treatments in the diabetespatients with breast cancer.
Authors: Alicia Beeghly-Fadiel; Nikhil K Khankari; Ryan J Delahanty; Xiao-Ou Shu; Yingchang Lu; Marjanka K Schmidt; Manjeet K Bolla; Kyriaki Michailidou; Qin Wang; Joe Dennis; Drakoulis Yannoukakos; Alison M Dunning; Paul D P Pharoah; Georgia Chenevix-Trench; Roger L Milne; David J Hunter; Hall Per; Peter Kraft; Jacques Simard; Douglas F Easton; Wei Zheng Journal: Int J Epidemiol Date: 2020-08-01 Impact factor: 7.196
Authors: David de Gonzalo-Calvo; Laura López-Vilaró; Laura Nasarre; Maitane Perez-Olabarria; Tania Vázquez; Daniel Escuin; Lina Badimon; Agusti Barnadas; Enrique Lerma; Vicenta Llorente-Cortés Journal: BMC Cancer Date: 2015-06-09 Impact factor: 4.430
Authors: Pik-Fang Kho; Frederic Amant; Daniela Annibali; Katie Ashton; John Attia; Paul L Auer; Matthias W Beckmann; Amanda Black; Louise Brinton; Daniel D Buchanan; Stephen J Chanock; Chu Chen; Maxine M Chen; Timothy H T Cheng; Linda S Cook; Marta Crous-Bous; Kamila Czene; Immaculata De Vivo; Joe Dennis; Thilo Dörk; Sean C Dowdy; Alison M Dunning; Matthias Dürst; Douglas F Easton; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Christine M Friedenreich; Montserrat García-Closas; Mia M Gaudet; Graham G Giles; Ellen L Goode; Maggie Gorman; Christopher A Haiman; Per Hall; Susan E Hankinson; Alexander Hein; Peter Hillemanns; Shirley Hodgson; Erling A Hoivik; Elizabeth G Holliday; David J Hunter; Angela Jones; Peter Kraft; Camilla Krakstad; Diether Lambrechts; Loic Le Marchand; Xiaolin Liang; Annika Lindblom; Jolanta Lissowska; Jirong Long; Lingeng Lu; Anthony M Magliocco; Lynn Martin; Mark McEvoy; Roger L Milne; Miriam Mints; Rami Nassir; Geoffrey Otton; Claire Palles; Loreall Pooler; Tony Proietto; Timothy R Rebbeck; Stefan P Renner; Harvey A Risch; Matthias Rübner; Ingo Runnebaum; Carlotta Sacerdote; Gloria E Sarto; Fredrick Schumacher; Rodney J Scott; V Wendy Setiawan; Mitul Shah; Xin Sheng; Xiao-Ou Shu; Melissa C Southey; Emma Tham; Ian Tomlinson; Jone Trovik; Constance Turman; Jonathan P Tyrer; David Van Den Berg; Zhaoming Wang; Nicolas Wentzensen; Lucy Xia; Yong-Bing Xiang; Hannah P Yang; Herbert Yu; Wei Zheng; Penelope M Webb; Deborah J Thompson; Amanda B Spurdle; Dylan M Glubb; Tracy A O'Mara Journal: Int J Cancer Date: 2020-08-07 Impact factor: 7.396