Anti-chloride Intracellular Channel Protein 1 (CLIC1) Antibodies Induce Tumour Necrosis and Angiogenesis Inhibition on In Vivo Experimental Models of Human Renal Cancer

Anticancer Res. 2022 Mar;42(3):1313-1325. doi: 10.21873/anticanres.15599.

Abstract

Background/aim: Chloride intracellular channel protein 1 (CLIC1) is known as a promoter of cancer progression, metastasis, and angiogenesis. Thus, CLIC1 could be a future therapeutic target. This study aimed to evaluate the effect of anti-CLIC1 antibodies on tumour cells and vessels of human renal cell carcinoma (RCC) in rabbit cornea and chick embryo chorioallantoic membrane (CAM) models.

Materials and methods: Human cc-RCC xenografts on rabbit cornea and CAM surface were performed. Anti-CLIC1 antibodies were applied for 5 consecutive days on both tumor models. We comparatively evaluated treated and untreated tumors by combining ultrasonography with microscopic techniques.

Results: RCC implants rapidly recruited blood vessels and had an exponential growth rate on both tumor models. Anti-CLIC1 antibodies suppressed tumor growth by inducing tumor cell necrosis. Tumor vessels regressed rapidly but not completely during anti-CLIC1 antibodies based therapy.

Conclusion: Anti-CLIC1 antibodies induced tumor necrosis and tumor vasculature regression in human cc-RCC xenografts in both in vivo experimental models.

Keywords: Anti-CLIC1 antibodies; chick embryo chorioallantoic membrane model; clear cell renal cell carcinoma (cc-RCC); cornea rabbit model.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents, Immunological / pharmacology*
  • Carcinoma, Renal Cell / blood supply*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chloride Channels / antagonists & inhibitors*
  • Chloride Channels / metabolism
  • Kidney Neoplasms / blood supply*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Molecular Targeted Therapy
  • Necrosis
  • Neovascularization, Pathologic*
  • Rabbits
  • Signal Transduction
  • Time Factors
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • CLIC1 protein, human
  • Chloride Channels