INTERPLAY OF FIBROBLASTS WITH ANAPLASTIC TUMOR CELLS PROMOTES FOLLICULAR THYROID CANCER PROGRESSION

ALAMINO,V; ZHAO, L; CHENG, S; ALAMINO,V; ZHAO, L; CHENG, S; GIUSIANO, L; STEMPIN, CC; PELLIZAS, C; FOZZATTI, L; GIUSIANO, L; VOLPINI, X; STEMPIN, CC; DONADÍO, AC; PELLIZAS, C; FOZZATTI, L; VOLPINI, X; DONADÍO, AC

Whasington, DC

Congreso; 88th Annual Meeting of the American Thyroid Association; 2018

Thyroid cancer is the most common endocrine malignancy. Anaplasticthyroid cancer is one of the most aggressive thyroid tumors. Ithas been widely described that activation of oncogenes and/or inactivationof tumor suppressor genes in tumor cells promotes tumorigenesis.The microenvironment of the tumor also plays a keyrole on cancer development and progression in a variety of tumors.However, the mechanisms by which tumor-stroma crosstalk in thyroidcancer remains poorly characterized. In this study we aimed tounderstand how interactions between fibroblasts and anaplasticthyroid cancer cells contribute to thyroid carcinogenesis process. Wefirst characterized the phenotypic changes of human fibroblastsin vitro through co-cultures by using transwells as well as by usinganaplastic thyroid cancer cells-derived conditioned media. We foundthat fibroblasts acquired an activated phenotype or also known ascancer-associated fibroblast phenotype after being in contact withsoluble factors secreted from anaplastic thyroid cancer cells, comparedto the fibroblasts in mono-cultures. All the changes were partlymediated through Src/Akt activation. Remarkably, conditioned mediaobtained from these activated fibroblasts promoted cell proliferationand invasion of follicular thyroid cancer cell line, FTC-133cells. Thus, a reciprocal and dynamic interaction exists between tumorand stromal cells, which results in the promotion of thyroidtumorigenesis process. The present studies have advanced the understandingof the molecular basis of tumor-stroma communications,enabling identification and targeting of tumor-supportive mechanismsfor novel treatment modalities.