Pankreas duktal adenokarsinomlarında kök hücre belirteci CD133 ve CXCR4/CXCL12 kompleksinin kötü prognoz ile ilişkisinin araştırılması/ Investigation of the Relationship Between Stem Cell Markers CD133 and CXCR4/CXCL12 Complex and Poor Prognosis in Pancreatic Ductal Adenocarcinomas

Abstract

Introduction and Purpose: Exocrine pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all pancreatic malignancies. PDAC has a high mortality rate and 5-year survival rate is 7%. It is expected to become the second cause of cancer related deaths by 2030. The primary treatment for this agressive malignancy is surgical resection. Unfortunately, due to the low early diagnosis rate, only 10-20% of patients are resectable. Even in operable cases, 5-year survival is low. One of the reasons for this poor prognosis is the high resistance of PDAC to chemotherapy. One of the underlying causes of chemotherapy resistance is cancer stem cells (CSC) and chemokines. The CSC's are responsible for tumor recurrence after initiation of the tumor, rapid growth with self-regeneration capacity, resistance to treatment, formation of metastases and recurrence after adjuvant therapy. CSC has been found in many malignant tumors, including pancreatic cancer. CD133 expression has been identified in pancreatic CSCs. Chemokines are the cytokines that regulate various phsiological and immune processes and also increase the growth, poliferation and metastasis of tumor cells. Chemokines display their above functions by binding to and activating chemokine receptors in the cell membrane. Chemokine receptor type 4 (CXCR4) is the suitable receptor for chemokine ligand 12. The CXCL 12/ CXCR4 complex is one of the most prominent chemokine moderators that make up the tumor microenvironment. The CXCR4/CXCL 12 chemokine complex has been found to play an important role in pancreatic cancer development, invasion, metastasis and treatment resistance.

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