An acidic microenvironment promotes lymphatic metastasis of melanoma by Thy-1 in endothelial cells and integrin αvβ3 in tumor cells

  • 0Department of Pathology, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan.

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Summary

This summary is machine-generated.

The study reveals that an acidic tumor microenvironment promotes melanoma lymphatic metastasis. Acid-induced Thy-1 in lymphatic cells and integrin αvβ3 in melanoma cells enhance cell adhesion, driving metastasis.

Area Of Science

  • Oncology
  • Cell Biology
  • Biochemistry

Background

  • Melanoma tissues often present an acidic microenvironment.
  • The impact of this acidity on melanoma's lymphatic metastasis remains largely unknown.
  • Lymphatic metastasis is a critical factor in melanoma patient prognosis.

Purpose Of The Study

  • To investigate the role of the acidic microenvironment in lymphatic endothelial cell function.
  • To explore the mechanisms by which acidity influences melanoma cell metastasis.

Main Methods

  • Gene expression profiling of human dermal lymphatic endothelial cells (HDLECs) under acidic conditions.
  • Immunohistochemical analysis in a mouse melanoma model.
  • In vitro cell adhesion assays and in vivo metastasis models.

Main Results

  • Acidic conditions increased Thy-1 expression in HDLECs in a time-dependent manner.
  • Integrin αvβ3 expression was upregulated in melanoma cells under acidic conditions.
  • Acidic conditions enhanced HDLEC-melanoma cell adhesion, mediated by Thy-1 and integrin αvβ3, and silencing integrin αv reduced metastasis.

Conclusions

  • Acid-induced Thy-1 in lymphatic endothelial cells and integrin αvβ3 in melanoma cells promote mutual adhesion.
  • This interaction contributes significantly to melanoma's lymphatic metastasis.
  • Targeting these interactions may offer therapeutic strategies for melanoma.

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