Smooth muscle actin‐expressing stromal fibroblasts in head and neck squamous cell carcinoma: Increased expression of galectin‐1 and induction of poor prognosis factors

Abstract

Tumor stroma is an active part influencing the biological properties of malignancies via molecular cross-talk. Cancer-associated fibroblasts play a significant role in this interaction. These cells frequently express smooth muscle actin and can be classified as myofibroblasts. The adhesion/growth-regulatory lectin galectin-1 is an effector for their generation. In our study, we set the presence of smooth muscle actin-positive cancer-associated fibroblasts in relation to this endogenous lectin and an in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence was highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor (p 5 4 3 10 28 ). To pinpoint further correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts. These activated genes (MAP3K2, TRIM23, PTPLAD1, FUSIP1, SLC25A40 and SPIN1) are related to known squamous-cell-carcinoma poor-prognosis factors, NF-jB upregulation and splicing downregulation. These results provide new insights into the significance of presence of myofibroblasts in squamous cell carcinoma.Increasing attention is being turned to the stroma part in carcinomas. It is formed by fibroblasts producing the extracellular matrix, macrophages and other inflammatory cells as well as blood/lymphatic capillaries. 1 Recent progress in cancer and skin cell biology has markedly changed our view on the functional significance of the stroma. Classically, the tumor stroma has been considered as a milieu suitable for growth of capillaries that guarantee the supply with oxygen and nutrients for the cancer epithelium. With the new data being accrued, the stroma can be described as an active microenvironment, which modulates the biology of the tumor including cancer stem (initiating) cells by mechanisms similar to the function of the niche in the case of tissue stem cells. 2 As a consequence, a focus of this research is given to the study of mutual epithelial-mesenchymal interactions. This interplay is known to be crucial for embryonic development, and a major role in the route of tumor progression is likely. 2,3 The fibroblasts of the stroma, that is, cancer-associated fibroblasts (CAF), frequently contain fibers of smooth muscle a-actin (SMA and ACTA2), showing notable similarities to myofibroblasts responsible for the contraction of a wound in the course of a healing process. 4 The origin of CAF is not

Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor‐associated fibroblasts in preclinical models

“…Several studies have demonstrated that fibroblasts isolated from tumors express α-smooth muscle actin (26,27) . Further, epithelial cells express cytokeratin-14 (28) .…”

Galectin-1 Couples Glycobiology to Inflammation in Osteoarthritis through the Activation of an NF-κB–Regulated Gene Network

“…These findings are consistent with reports implicating Galectin-1 in the positive regulation of NF-kB gene targets, in contrast to the well-documented anti-inflammatory role. In fact, in human mesenchymal stem cells, Galectin-1 activates NF-kBdependent fibronectin, laminin-5, and MMP-2 expression (50); in stimulated rat pancreatic stellate cells, Galectin-1 increased the production of chemokines (51,52); and in tissue of squamous cell, head and neck carcinomas factors associated with NF-kB activation and for poor prognoses such as TRIM23 and MAP3K2 (53).…”

Myofibroblasts from salivary gland adenoid cystic carcinomas promote cancer invasion by expressing MMP2 and CXCL12

“…Until now, surgical excision has been the most common choice for ACC treatment, and adjunctive radiation therapy has been shown to slightly improve patient survival in some cases . Recent attempts to elucidate tumour behaviour have focused on the stroma, which is considered to be important for tumour growth and invasion . In this study, we tried to determine whether the stromal cells contribute to the invasive ability of ACCs.…”