A novel role of thrombospondin-1 in cervical carcinogenesis: inhibit stroma reaction by inhibiting activated fibroblasts from invading cancer

Carcinogenesis
Ming-Ping WuCheng-Yang Chou

Abstract

Thrombospondin (TSP)-1, a potent angiogenesis inhibitor, has been shown to exert different biological functions on various cell types. Here, we investigate the role of TSP-1 in tumor-stroma reaction, which is mainly characterized by fibroblast activation to create a permissive microenvironment for tumor progression. Immunohistochemistry examinations in the human surgical specimens have shown that a downregulation of TSP-1 during the progression of cervical carcinogenesis was accompanied by an emergence in the upregulation of stroma markers, alpha-smooth muscle actin (alpha-SMA) and desmin. Transfection of SiHa cervical cancer cells with a plasmid expressing the TSP-1 protein exhibited antiangiogenic activity in vitro and resulted in reduced tumor growth in severe combined immunodeficiency (SCID) mice, which was accompanied by a decrease in tumor vascularization and lower expressions of alpha-SMA and desmin than those in the vector controls. Transfection with TSP-1 and purified TSP-1 added to NIH3T3 cells did not alter the protein levels of alpha-SMA and desmin but significantly inhibited matrix metalloprotease-2 activity. Transforming growth factor-beta (TGF-beta), a major factor in the activation of fibroblasts, increased alph...Continue Reading

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Nov 22, 2011·Cancer Metastasis Reviews·Paolo Cirri, Paola Chiarugi
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May 1, 2021·International Journal of Molecular Sciences·Sukhbir KaurDavid D Roberts

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