Pancreatic Cancer Tissue Exosome Research and Application

Pancreatic cancer is a malignant tumor originating from the ductal epithelium and alveolar cells of the pancreas, mainly ductal cell carcinoma, and to a lesser extent, alveolar cell carcinoma, and rarely pancreatic acanthoma and cystic adenocarcinoma. Studying the role of pancreatic cancer tissue exosomes in pancreatic cancer proliferation, metastasis, and chemoresistance provides new insights into the diagnosis and treatment of pancreatic cancer. Creative Biolabs is proud to offer a range of research services in pancreatic cancer tissue exosomes with the most competitive quality.

Tissue Exosomes and Pancreatic Carcinogenesis

Pancreatic cancer contains extensive mesenchymal tissue, which accounts for approximately 90% of the tumor volume and is capable of stimulating cancer cell invasion and escaping immune surveillance from the host. Among them, pancreatic stellate cells are as one of the critical pancreatic mesenchymal cells. Studies have shown that pancreatic cancer cells secrete exosomes that stimulate activation and pro-fibrotic processes in pancreatic stellate cells, including direct promotion of cancer cell proliferation, collagen production, and α-SMA (α-smooth muscle actin) mRNA expression. This dynamic interaction between pancreatic stellate cells and pancreatic cancer cells promotes the formation of a pancreatic cancer microenvironment. In addition, multiple cargoes loaded in pancreatic cancer exosomes that are associated with pancreatic cancer metastasis have been identified. For example, pancreatic cancer exosomes, upon selective uptake by hepatic Kupffer cells, mediated upregulation of TGF-β and expression of fibronectin by hepatic stellate cells. Fibronectin is deposited in the liver, creating a fibrotic microenvironment that promotes the accumulation of bone marrow-derived macrophages and neutrophils in the liver, thus creating a microenvironment conducive to the metastasis of disseminated pancreatic cancer cells, i.e., ecotropic metastasis. Also, pancreatic cancer produces miRNA-21-rich exosomes to promote metastasis of hypoxic tumor cells, while miRNA-301a-rich exosomes mediate the polarization of M2-type macrophages and the formation of an immunosuppressive state microenvironment via the PTEN/PI3Kγ pathway.

Tissue Exosomes and Chemotherapy Resistance

With the activation of oncogenic miRNAs, anti-apoptotic enzymes, and signaling pathways associated with cellular drug resistance, pancreatic cancer cells have gradually developed resistance to chemotherapy. Besides, the mesenchymal tissue of pancreatic cancer is featured low perfusion and hypoxia, and the dense mesenchyme can affect the release of chemotherapeutic drugs through physical barriers, high mesenchymal pressure, compressed blood vessels, and thick mesenchymal cells. Therefore, resistance to chemotherapeutic agents remains the greatest obstacle to the efficacy and prognosis of chemotherapy for pancreatic cancer. Pancreatic cancer exosomes have been shown to enhance chemotherapy resistance through various mechanisms. For example, pancreatic cancer tissue exosomes can reduce the apoptosis of tumor cells during chemotherapy by inhibiting the expression of apoptosis-inhibitory proteins. Moreover, miRNA-155 in pancreatic cancer tissue exosomes can inhibit the activity of the rate-limiting enzyme deoxycytidine kinase, thereby interfering with the metabolic process of chemotherapeutic agents and enhancing the drug resistance of tumor cells. In addition, exosomes secreted by tumor-associated fibroblasts in the pancreatic cancer microenvironment induce epithelial-mesenchymal transition and promote the expansion of the drug-resistant cancer cell population during chemotherapy by significantly increasing the expression level of transcription factor snail.

Fig.1 Intercellular crosstalk in pancreatic cancer. (Sun, 2020)

Studying the function and mechanism of pancreatic cancer tissue exosomes in pancreatic carcinogenesis, metastasis, and chemoresistance is beneficial in guiding the screening of reliable markers for early diagnosis and prognostic assessment of pancreatic cancer. In particular, proteomic and miRNA sequencing analysis of pancreatic cancer tissue exosomes improves the detection of key lesion molecules. Creative Biolabs is dedicated to providing customized and comprehensive solutions for pancreatic cancer tissue exosomes. Please feel free to contact us for more information.

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