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Updated: Jun 25, 2026

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
09:53

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus

Published on: August 25, 2017

ID2-VEGF-related pathways in the pathogenesis of Kaposi's sarcoma: a link disrupted by rapamycin

G Stallone1, B Infante, P Pontrelli

  • 1Department of Biomedical Sciences, Section of Nephrology, University of Foggia, Italy. g.stallone@unifg.it

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|March 6, 2009
PubMed

Insights

Rapamycin (RAPA) treatment normalizes Id2 expression and reduces lymphangiogenesis in Kaposi's sarcoma (KS). This suggests a new mechanism for RAPA's anti-cancer effects in post-transplant KS by targeting Id2 and lymphatic vessel growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Id-proteins regulate cell differentiation and cell-cycle progression; Id2 down-regulation is crucial for differentiation.
  • Aberrant Id2 activity disrupts tumor suppressor pathways and promotes vascular endothelial growth factor (VEGF) expression, implicated in Kaposi's sarcoma (KS).
  • Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is a marker for lymphatic endothelial cells and is found on KS spindle cells.

Purpose of the Study:

  • To investigate the effects of Rapamycin (RAPA) on Id2 expression and de novo lymphangiogenesis in transplantation-associated KS and cultured KS cells.
  • To explore the potential molecular mechanisms underlying RAPA's anti-neoplastic effects in post-transplant KS.

Main Methods:

  • Evaluation of Id2, VEGFR-3, and LYVE-1 expression in KS tissues and cultured KS cells before and after RAPA treatment.
  • Assessment of RAPA's effect on Id2 expression in KS cells under basal and VEGF-stimulated conditions.
  • Analysis of co-localization of Id2, VEGFR-3, and LYVE-1 to infer associations.

Main Results:

  • Id2, VEGFR-3, and LYVE-1 were upregulated in KS and normalized after RAPA treatment.
  • Co-localization of Id2, VEGFR-3, and LYVE-1 suggests a link between Id2 and lymphangiogenesis.
  • RAPA inhibited Id2 expression in KS cells in vitro, both in basal and VEGF-stimulated states.

Conclusions:

  • Data suggest a novel molecular mechanism for RAPA's antineoplastic activity in post-transplant KS.
  • RAPA appears to exert its effects by down-regulating Id2 expression and inhibiting lymphangiogenesis.
  • Targeting Id2 may represent a therapeutic strategy for managing KS.

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