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Title: Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment

The turnover of extracellular matrix liberates various cryptic molecules with novel biological activities. Endostatin is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of collagen XVIII. Although there are a large number of studies on its anti-tumor effects, the molecular mechanisms are not yet completely understood, and the reasons why endostatin has not been successful in clinical trials are unclear. Research has mostly focused on its anti-angiogenic effect in tumors. Here, we aimed to elucidate how endostatin affects the behavior of aggressive tongue HSC-3 carcinoma cells that were transfected to overproduce endostatin. Endostatin inhibited the invasion of HSC-3 cells in a 3D collagen–fibroblast model. However, it had no effect on invasion in a human myoma organotypic model, which lacks vital fibroblasts. Recombinant endostatin was able to reduce the Transwell migration of normal fibroblasts, but had no effect on carcinoma associated fibroblasts. Surprisingly, endostatin increased the proliferation and decreased the apoptosis of cancer cells in organotypic models. Also subcutaneous tumors overproducing endostatin grew bigger, but showed less local invasion in nude mice xenografts. We conclude that endostatin affects directly to HSC-3 cells increasing their proliferation, but its net effect on cancer invasion seem to depend on the cellularmore » composition and interactions of tumor microenvironment. - Highlights: • Endostatin affects not only angiogenesis, but also carcinoma cells and fibroblasts. • Endostatin increased carcinoma cell proliferation, but decreased 3D invasion. • The invasion inhibitory effect was sensitive to the microenvironment composition. • Fibroblasts may be a factor regulating the fluctuating roles of endostatin.« less
Authors:
 [1] ;  [2] ;  [3] ;  [2] ; ;  [1] ;  [2] ;  [4] ;  [1] ;  [2] ; ;  [3] ;  [2] ;  [1] ;  [2] ;  [2] ;  [5] ;  [1] ;  [2]
  1. Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland)
  2. (Finland)
  3. Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu (Finland)
  4. Department of Oral and Maxillo-facial Diseases, University of Helsinki, Helsinki University Central Hospital (Finland)
  5. (Brazil)
Publication Date:
OSTI Identifier:
22462314
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 336; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; APOPTOSIS; AUGMENTATION; CARCINOMAS; CELL PROLIFERATION; COLLAGEN; FIBROBLASTS; HUMAN POPULATIONS; LABELLING; MICE; MIGRATION; MOLECULES