MURAGAKI Yoshihiro
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Visiting Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells
Journal Formal name：Exp Cell Res
ISSN code：1090-2422(Electronic)0014-4827 (Linking)
Domestic / ForeginForegin
Volume, Issue, Page 345(2),pp.180-189
Author and coauthor NAKANISHI Masako†, MORITA Yoshihiro, HATA Kenji, MURAGAKI Yoshihiro
Publication date 2016/07
Summary Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5'-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-kappaB was induced by acidic conditions, and inhibition of NF-kappaB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis.
DOI 10.1016/j.yexcr.2016.06.006
Document No. 27312995