Chitinase-3-like Protein 1 (YKL-40) Expression in Squamous Cell Skin Cancer

Abstract

Abstract. Background/Aim: YKL-40 plays a role in proliferation and differentiation of malignant cells. The aim of this study was to examine whether YKL-40 is expressed in cutaneous squamous cell carcinoma (SCC). Materials andChitinase-3-like protein 1 (YKL-40) is a glycoprotein discovered over 10 years ago (1). This protein belongs to the glycosyl hydrolase family 18, together with bacterial chitinases and several mammalian chitinase-like proteins (1). The biological function of YKL-40 is not fully understood; however, the studies conducted so far suggest its role in inflammation, cell differentiation, tissue remodeling and cancer growth. It is expressed and released by activated neutrophils, monocytes and macrophages (2). Various studies have reported its secretion by activated cells in inflammatory diseases, such as arthritic chondrocytes, arteritic vessels in giant cell arteritis, liver cells in viral hepatitis or atheromatous plaques and inflamed synovial membrane (3-5).The role of YKL-40 in cancer growth is not clearly understood; however, many reports imply that this protein plays a role in proliferation and differentiation of malignant cells. Its ability to activate many pathways, including the phosphoinositide-3-kinase pathway, suggests the possibility of inducing cancer cell proliferation and acting as an antiapoptotic and survival factor (6). Moreover, this protein is an adhesion and migration factor for vascular smooth muscle cells and promotes the migration of vascular endothelial cells (7). It is also suggested that YKL-40 may influence local synthesis of hyaluronan and act as an anticatabolic factor, preserving the extracellular tissue from destruction (8). These findings lead to the conclusion that YKL-40 stimulates tumor angiogenesis, promotes inflammation in tumor microenvironment and influences remodeling of the extracellular matrix, thus providing a better understanding of its role in cancer growth and metastasis (9).Elevated serum levels of YKL-40 have been reported in lung, bladder, ovarian, endometrial, renal, colorectal, breast cancers as well as in melanoma and other malignancies, and have been correlated with the stage of cancer and overall survival (10-18). Moreover, YKL-40 expression has been shown in the cells of many malignancies, such as melanoma, renal cell cancer, endometrial cancer, breast cancer, glial tumors, osteosarcoma, soft tissue sarcomas or squamous cell carcinomas of head, neck and esophagus (14,17,(19)(20)(21)(22)(23)(24). It has been even suggested that YKL-40 can serve as a new target for anticancer therapy (9,25). To the best of our knowledge there are no studies of YKL-40 expression in non-melanoma skin cancers. Therefore, the aim of this study was to examine whether YKL-40 is expressed in the tumor tissue of cutaneous squamous cell carcinoma (SCC). 4753This article is freely accessible online.

Mechanistic Interrogation of Cell Transformation in Vitro: The Transformics Assay as an Exemplar of Oncotransformation

“…n.1-3-5). This gene modulation has been already proposed in other studies as a potential link between the molecular microenvironment related to in ammation and cells transformation 16,17 . Moreover this gene has been shown to be secreted by Cancer Associated Fibroblasts (CAFs) in breast carcinomas during both early and advanced stages, and to play a central role in tumor promotion, producing a pro-in ammatory and immunosuppressed microenvironment 16,17 .…”

Mechanistic Interrogation of Cell Transformation In Vitro: The Transformics Assay as an Exemplar of Oncotransformation

“…It is also worth noting the Chil1 (Chitinase-like 1, also known as Chi3l1) differential gene expression (FC: +20.65; Table 3: GO processes i.e., n.1-3-5). This gene modulation has been already proposed in other studies as a potential link between the molecular microenvironment related to inflammation and cells transformation [30,31]. Moreover, this gene has been shown to be secreted by Cancer Associated Fibroblasts (CAFs) in breast carcinomas during both early and advanced stages, and to play a central role in tumor promotion, producing a pro-inflammatory and immunosuppressed microenvironment [30,31].…”

Oligodendrocyte Progenitor Cells Increase Chi3l1 Secretion in exosome to Activate Myh9 and Promote Proliferation through Connexin47 Connected to Astrocytes

“…Chi3l1 is a member of the glycoprotein hydrolase 18 family and has the ability to bind chitin but has no enzymatic activity [51][52]. Chi3l1 is a tumor-associated factor that is highly expressed in various tumor cells by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT and nuclear factor (NF)-κB pathways to promote tumor growth, invasion and metastasis [26,[53][54][55]. It is also an in ammatory factor that activates the in ammatory response [19,[56][57][58].…”