The role of transforming growth factor beta in carcinogenesis and metastasis processes in thyroid carcinomas. A review of the literature and our own data

Abstract

Transforming growth factor beta (TGF-β) is critical for numerous physiological and pathological processes. It influences cell growth, differentiation, migration, apoptosis, immune regulation, and tissue repair through complex signaling pathways, acting on both healthy and diseased cells. The role of TGF-β in carcinogenesis is ambiguous. Initially, it acts through the canonical pathway as atumor suppressor, inhibiting cell growth, promoting apoptosis, and maintaining genetic stability. In advanced stages of cancer, TGF-β signaling becomes a potent promoter of malignancy, contributing to several key processes which stimulate cancer progression and complicate treatment. TGF-β plays a crucial role in the development of metastases by inducing EMT, a process in which epithelial cells lose their adhesiveness and polarity, acquiring migratory and
invasive characteristics typical for mesenchymal cells. TGF-β has become an important biomarker in cancer diagnosis due to its key role in tumor biology. As a multifunctional cytokine, it is involved in cell growth, differentiation, and immunomodulation. Altered expression and activity of TGF-β are often associated with cancer progression. Elevated levels of TGF-β have been found in various types of cancer, including thyroid cancer. TGF-β also promotes angiogenesis, maturation, and stabilization of newly formed blood vessels, which supports tumor growth and metastasis. TGF-β1 is a promising marker of metastasis and a factor in the formation of radioiodine-resistant metastases in thyroid carcinomas. According
to our data, the TGF-β1 concentration in tumor tissue of papillary thyroid carcinoma (PTC) with metastases was almost 5-fold higher than in conditionally normal tissue and 3-fold higher than in РTC tissues without metastases. Plasma TGF-β1 levels were also significantly higher in patients with РTC and metastases than in healthy individuals and PTC patients without metastases. Therefore, TGF-β may be an important marker of metastatic process in thyroid tumors in the preoperative period.