[Promotion of growth of human breast cancer cells MDA231 by human sperm membrane-bound hyaluronidase: an experimental study].
OBJECTIVE
To study the mechanism how human sperm membrane-bound hyaluronidase (PH20) promotes the gowth of human breast cancer.


METHODS
Full-length cDNA of human PH20 was transfected into human breast cancer cell line MDA231. The transfectant MDA231-PH20 was then implanted into the chorio-allantoic membrane (CAM) of chicken embryo to form a tumor. Four days after implantation, the tumors were resected to be weighed. The angiogenesis in tumor tissue was examined by immunohistochemistry. Trans-well cell culture was used to study the effect of MDA231-PH20 on the growth of adult bovine aortic endothelial cells (ABAE). The expression of fibroblast growth factor-2 (FGF-2) in the tumor cells was investigated by Western blotting. ELISA was used to examine the secretion of FGF-2 and hyaluronic acid. The same amount of empty vector pcDNA3, instead of PH20, was transfected into human breast cancer cell line MDA231 as control group.


RESULTS
The average weight of tumor four days after implantation was 44.7 mg +/- 10.2 mg in the MDA231-PH20 group, and was 21.3 mg +/- 2.8 mg in the control group (t = 2.418, P = 0.038). Neogenetic vessels increased remarkably in MDA231-PH20 tumor tissues. The expression of FGF-2 protein was much higher in MDA231-PH20 cells. The FGF content and HA secretion were higher in the MDA231-PH20 group than in the control group (8.10 pg/ml +/- 1.56 pg/ml vs. 3.94 pg/ml +/- 0.82 pg/ml, and 1 220 ng/ml +/- 254 ng/ml vs. 462 ng/ml +/- 96 ng/ml, all P < 0.01). The growth of ABAE cells was significantly accelerated after co-culture with MDA231-PH20 transfectant.


CONCLUSIONS
PH20 may promote the growth of human breast cancer by accelerating the release of FGF-2 from tumor cells, decomposing HA into small fragments, and promoting angiogenesis.
Gao
Feng
F
Department of Clinical Laboratory, Shanghai No. 6 People's Hospital, Shanghai 200233, China.
Zhang
Lurong
L
Underhill
Charles B
CB
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D013094:Spermatozoa / Q000201:enzymology*; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D016222:Fibroblast Growth Factor 2; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase