A chondroitin sulfate proteoglycan 4‑specific monoclonal antibody inhibits melanoma cell invasion in a spheroid model

Karolina Uranowska, Mahzeiar Samadaei, Tanja Kalic, Matthias Pinter, Heimo Breiteneder, Christine Hafner

Research output: Journal article (peer-reviewed)Journal article

2 Citations (Scopus)

Abstract

The overexpression of chondroitin sulfate proteoglycan 4 (CSPG4) is associated with several tumor types, including malignant melanoma, squamous cell carcinoma, triple‑negative breast carcinoma, oligodendrocytomas or gliomas. Due to its restricted distribution in normal tissues, CSPG4 has been considered a potential target for several antitumor approaches, including monoclonal antibody (mAb) therapies. The aim of the present study was to characterize the impact of the CSPG4‑specific mAb clone 9.2.27 on its own or in combination with the commonly used BRAF‑selective inhibitor, PLX4032, on different functions of melanoma cells to assess the potential synergistic effects. The BRAF V600‑mutant human melanoma cell lines, M14 (CSPG4‑negative) and WM164 (CSPG4‑positive), were exposed to the CSPG4‑specific 9.2.27 mAb and/or PLX4032. Cell viability and colony formation capacity were evaluated. A 3D‑cell culture spheroid model was used to assess the invasive properties of the treated cells. In addition, flow cytometric analysis of apoptosis and cell cycle analyses were performed. Incubation of the WM164 cell line with CSPG4‑specific 9.2.27 mAb decreased viability, colony formation ability and the invasive capacity of CSPG4‑positive tumor cells, which was not the case for the CSPG4‑negative M14 cell line. Combined treatment of the WM164 cells with 9.2.27 mAb plus PLX4032 did not exert any significant additional effect in comparison to treatment with PLX4032 alone in the clonogenic and invasion assays. M14 cell cycle distribution was not influenced by the CSPG4‑specific 9.2.27 mAb. By contrast, the exposure of WM164 cells to the mAb resulted in an arrest of the cells in the S phase. Moreover, combined treatment of the WM164 cells led to a significantly increased accumulation of cells in the subG1 phase, combined with a decrease of cells in the G2/M phase. On the whole, findings of the present study indicate that the CSPG4‑specific 9.2.27 mAb exerts an anti‑invasive effect on CSPG4‑positive melanoma spheroids, which is not enhanced by BRAF inhibition. These findings provide the basis for further investigations on the effects of anti‑CSPG4‑based treatments of CSPG4‑positive tumors.

Original languageEnglish
Article numberA1
JournalInternational Journal of Oncology
Volume59
Issue number3
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Antibodies, Monoclonal/pharmacology
  • Cell Cycle/drug effects
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Survival/drug effects
  • Chondroitin Sulfate Proteoglycans/metabolism
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Melanoma/drug therapy
  • Membrane Proteins/metabolism
  • Mutation
  • Proto-Oncogene Proteins B-raf/genetics
  • Spheroids, Cellular/cytology
  • Tumor Cells, Cultured
  • Vemurafenib/pharmacology
  • BRAF inhibitor
  • Monoclonal antibody
  • Melanoma
  • Cell invasion inhibition
  • Spheroids
  • BRAF-mutated melanoma
  • CSPG4-positive tumors
  • CSPG4-specific antibody
  • CSPG4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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