Increase of metalloproteinases (MMPs) activity and migratory ability of thyroid tumor cells induced by tumor cell-fibroblast interaction

DELLA VEDOVA AB; REMEDI MM; GILARDONI M; MASINI-REPISO AM; PELLIZAS C; DONADIO AC

Florianopolis

Congreso; XV Latin American Thyroid Congress; 2013

Sociedad Latinoamericana de Tiroides

Tumors are composed of two discrete but interactive compartments, parenchyma and stroma. The tumor cells themselves are the parenchyma, whereas the tumor stroma, or supporting tissue, is composed of endothelial cells, pericytes, invading inflammatory cells and leucocytes, fibroblasts and extensive extracellular matrix (ECM) components. The importance of the tumor stroma in cancer growth, invasion and metastasis is a fascinating and fundamental area of investigation. Recent studies indicate that the tumor stroma does not exist simply as a passive support structure, but rather plays an active role in tumor progression. [1,2]. Invasion involves changes in tumor cell adherence to other cells and to the ECM, proteolytic degradation of surrounding ECM and motility to physically propel a tumor cell through the stroma. The matrix metalloproteinases (MMPs) represent the most prominent family of proteinases associated with tumorigenesis. In addition to their role in ECM turnover and cancer cell migration, MMPs regulate signaling pathways that control cell growth, infammation, or angiogenesis [3]. Cancer-associated fibroblasts are essential for tumor progression providing both a functional and structural supportive environment, as well as an increase in metastatic potential by enhancing matrix degradation and angiogenesis through the production of MMPs and various cytokines or growth factors [4]. Using a rat thyroid tumor model, Saitoh and coworkers [5] demonstrated that fibroblasts (Fb), confer growth-promoting advantage to thyroid carcinoma cells. However, the role of thyroid tumor-Fb interaction in the invasive and migratory ability of thyroid tumor cells remains unknown. In the present work, using an in vitro thyroid tumor model, we analyse MMP2 and MMP9 expression and activity induced by tumor-Fb interaction. Thyroid tumor cell migration, induced by soluble factors present in Fb or Fb-thyroid tumor cells co-culture supernatants, was also analysed.