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PMID:20133819

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Citation

Heishi, T, Hosaka, T, Suzuki, Y, Miyashita, H, Oike, Y, Takahashi, T, Nakamura, T, Arioka, S, Mitsuda, Y, Takakura, T, Hojo, K, Matsumoto, M, Yamauchi, C, Ohta, H, Sonoda, H and Sato, Y (2010) Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis. Am. J. Pathol. 176:1950-8

Abstract

During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.

Links

PubMed PMC2843483 Online version:10.2353/ajpath.2010.090829

Keywords

Angiogenesis Inhibitors/pharmacology; Animals; Cell Cycle Proteins/biosynthesis; Cell Line, Tumor; Humans; Lymphangiogenesis; Lymphatic Metastasis/pathology; Male; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Neovascularization, Pathologic; Recombinant Proteins/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:VEGFA

acts_upstream_of_or_within

GO:1901492: positive regulation of lymphangiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(EMAPA:17161)

Seeded From UniProt

complete

MOUSE:VASH1

acts_upstream_of_or_within

GO:1901491: negative regulation of lymphangiogenesis

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q7L8A9

P

Seeded From UniProt

complete

MOUSE:VEGFA

acts_upstream_of_or_within

GO:0045766: positive regulation of angiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:VEGFA

acts_upstream_of_or_within

GO:1901492: positive regulation of lymphangiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

regulates_o_occurs_in:(EMAPA:17161)

Seeded From UniProt

complete

MOUSE:VEGFC

acts_upstream_of_or_within

GO:1901492: positive regulation of lymphangiogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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