Hyaluronan promotes tumor lymphangiogenesis and intralymphantic tumor growth in xenografts.
Hyaluronan (HA), a high molecular weight glycosaminoglycan in the extracellular matrix, has been implicated in the promotion of malignant phenotypes, including tumor angiogenesis. However, little is known about the effect of HA on tumor-associated lymphangiogenesis. In this study, mouse hepatocellular carcinoma Hca-F cells combined with or without HA were injected subcutaneously into C3H/Hej mice, then angiogenesis and lymphangiogenesis of implanted tumors were examined by immunostaining for platelet-endothelial cell adhesion molecule-1 and lymphatic vascular endothelial hyaluronan receptor-1 respectively. Interestingly, we found HA promotes tumor lymphangiogenesis and the occurrence of intratumoral lymphatic vessels, but has little effect on tumor angiogenesis. Moreover, HA also promotes intralymphatic tumor growth, although it is not sufficient to potentiate lymphatic metastasis. These results suggest that HA, which is elevated in most malignant tumor stroma, may also play a role in tumor progression by promoting lymphangiogenesis.
Guo
Li-Xia
LX
Laboratory of Biotherapy, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Zou
Ke
K
Ju
Ji-Hang
JH
Xie
Hong
H
D000818:Animals; D006023:Glycoproteins / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000494:pharmacology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D008207:Lymphatic Metastasis / Q000473:pathology / Q000503:physiopathology*; D042601:Lymphatic Vessels / Q000473:pathology*; D026901:Membrane Transport Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology*; D014183:Transplantation, Heterologous / Q000473:pathology*
D006023:Glycoproteins; D006820:Hyaluronic Acid; D026901:Membrane Transport Proteins; C492273:LYVE1 protein, mouse