Proteoglycans and their functions in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that has a poor prognosis. Its high lethality is mainly due to the lack of symptoms at early stages, which culminates in diagnosis at a late stage when the tumor has already metastasized. Unfortunately, the common cancer biomarkers have low sensitivity and specificity in esophageal cancer. Therefore, a better understanding of the molecular mechanisms underlying ESCC progression is needed to identify novel diagnostic markers and therapeutic targets for intervention. The invasion of cancer cells into the surrounding tissue is a crucial step for metastasis. During metastasis, tumor cells can interact with extracellular components and secrete proteolytic enzymes to remodel the surrounding tumor microenvironment. Proteoglycans are one of the major components of extracellular matrix. They are involved in multiple processes of cancer cell invasion and metastasis by interacting with soluble bioactive molecules, surrounding matrix, cell surface receptors, and enzymes. Apart from having diverse functions in tumor cells and their surrounding microenvironment, proteoglycans also have diagnostic and prognostic significance in cancer patients. However, the functional significance and underlying mechanisms of proteoglycans in ESCC are not well understood. This review summarizes the proteoglycans that have been studied in ESCC in order to provide a comprehensive view of the role of proteoglycans in the progression of this cancer type. A long term goal would be to exploit these molecules to provide new strategies for therapeutic intervention.

Network analysis of genes associated with esophageal squamous cell carcinoma progression

“…15 Metastasis is the process that cancer cells invaded into surrounded tissues. 7 In patients with EC receiving…”

“…LNM is a significant sign of cancer spread and a marker for poor clinical outcomes in numerous cancers, including EC 15. Metastasis is the process that cancer cells invaded into surrounded tissues 7. In patients with EC receiving neoadjuvant chemoradiation therapy, LNM is one of the crucial factors associated with overall survival 16.…”

“…6 As symptoms such as difficulty and pain in swallowing, loss of body weight, and heartburn are noticed, this disease is mostly diagnosed in the late stage when lymph node metastasis (LNM) is likely presented. 7 Despite advances in surgical treatment and multimodality therapies, patients with late clinical presentation of EC have poor prognosis. 8 Therefore, it is of clinical significance to improve the understanding about the molecular determinants of ESCC development for shaping new diagnostic approaches and developing new therapeutic modalities.…”

“…Unfortunately, early diagnosis of this disease is not easy as the clinical symptoms are not obvious and most of the cases are diagnosed at the advanced stage 6. As symptoms such as difficulty and pain in swallowing, loss of body weight, and heartburn are noticed, this disease is mostly diagnosed in the late stage when lymph node metastasis (LNM) is likely presented 7. Despite advances in surgical treatment and multimodality therapies, patients with late clinical presentation of EC have poor prognosis 8.…”

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights

“…ECMs enriched with PGs are associated with malignant transformation, inflammatory infiltration in the TME, and tumor aggressiveness ( 24 , 28 ). PGs are implicated in cell migration/invasion and alteration of TME in different tumors such as colorectal carcinoma, esophageal carcinoma, hepatocellular carcinoma, and breast carcinoma ( 29 – 32 ). In all these carcinomas, targeting PGs may provide new therapeutic approaches in the future.…”