The role of glial cell line‐derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells

Funahashi, Hitoshi; Okada, Yuji; Sawai, Hirozumi; Takahashi, Hiroki; Matsuo, Yoichi; Takeyama, Hiromitsu; Manabe, Tadao

doi:10.1002/jso.20277

Cited by 43 publications

(24 citation statements)

References 18 publications

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“…Moreover, GFRA1 (GDNF family receptor alpha-1) is a potent neurotrophic factor that plays a key role in the control of neuron survival and differentiation. Somewhere, this gene is introduced as a function of age [36]. Also, MTHFR (methylenetetrahydrofolate reductase) was proposed to participate in metabolic pathway.…”

Section: Discussionmentioning

confidence: 99%

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Naderi

Mostafaei

Pourshams

et al. 2014

BioMed Research International

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Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Naderi

Mostafaei

Pourshams

et al. 2014

BioMed Research International

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“…A common finding in pancreatic adenocarcinoma is invasion of the intrapancreatic perineural space and the extrapancreatic retroperitoneal nerve plexus, and perineural invasion is an important prognosis factor in pancreatic cancer (8,62). Several lines of evidence have recently suggested that GDNF signaling may be associated with regulation of the invasive potential in human pancreatic cancer cells (27,28,64,82). The expression of MMP-2 and MMP-9 correlates with the degree of pancreatic cancer cell and lymphoid invasion (61,101), and GDNF stimulates both the expression and the enzymatic activity of MMP-9 in pancreatic cancer cells (64).…”

Section: Discussionmentioning

confidence: 99%

Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression

Kim

Acharya

et al. 2009

Molecular and Cellular Biology

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The major human apurinic and apyrimidinic (AP) endonuclease 1 Ape1 (also known as Redox factor 1 [Ref-1]), which is homologous to Escherichia coli exonuclease III, plays a key role in both short-patch and long-patch base excision repair (20,40). It cleaves the AP sites in DNA and allows them to be repaired by other enzymes involved in base excision repair (16,23,24). The AP sites can be formed by chemical hydrolysis, the oxygen metabolism, ionizing radiation, UV irradiation, alkylating agents, or oxidizing agents (16,53). In addition, AP sites can also arise spontaneously, where it has been estimated that 20,000 purine samples and 500 pyrimidines are lost in each 24-h cell cycle in human cells (52). The presence of AP sites blocks DNA replication, leading to DNA breakage, mutagenicity, and cytotoxicity. Ape1/Ref-1 contributes to more than 95% of the total cellular AP site-specific activity (12), which is consistent with Ape1/Ref-1 being essential for maintaining the genomic stability. (32,35,73). Studies have reported elevated Ape1/Ref-1 levels or altered subcellular localization in various types of cancers, such as epithelial ovarian cancers, cervical cancers, prostate cell tumors, melanoma, gliomas, rhabdomyosarcoma, and germ cell tumors, which are associated with tumor resistance and progression (7,21,22,43,74,99,100). Ape1/Ref-1 is highly expressed in selected regions of the central nervous system (68,95). A reduction in Ape1/ Ref-1 expression occurs in the hippocampus after hypoxicischemic injury (93), in the cortex after compression injury (49), and in the spinal cord after ischemia (76). In addition,

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“…7 Cell migration has also shown to be increased by conditioned medium from GDNF-treated cells that expressed RET and GFRα1, and the increase in integrin expression induced by GDNF signalling through the GDNF receptor strongly influenced invasion and adhesion to the extracellular membrane by pancreatic cancer cells. 23 We conclude that GDNF may play an important role in the proliferation and metastasis of pancreatic cancer, especially in patients with perineural invasion. Furthermore, strongly positive expression of GDNF may be an indication for early intensified radiotherapy.…”

Section: Over-expression Of Gdnf and Ret In Pancreatic Cancermentioning

confidence: 69%

The Relationship between Over-expression of Glial Cell-derived Neurotrophic Factor and Its RET Receptor with Progression and Prognosis of Human Pancreatic Cancer

Zeng¹,

Cheng²,

Zhu³

et al. 2008

J Int Med Res

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We used immunohistochemical staining to assess protein over-expression of glial cell-derived neurotrophic factor (GDNF) and its RET receptor tyrosine kinase in patients with pancreatic cancer and benign pancreatic neoplasm, and assessed correlations with clinicopathological features and prognosis. Surgically resected pancreatic cancer patients (40/58, 68.9%) showed positive GDNF immunostaining, a significantly higher frequency than in patients with benign pancreatic tumour (3/11, 27.3%). Intrapancreatic neural invasion by cancer cells was significantly related to over-expression of GDNF. Strongly positive expression of GDNF was significantly more frequent than lesser grades of expression in patients with severe back pain before and 12 months after surgery. Expression of RET was significantly related to lymphatic invasion, survival rate after tumour resection and degree of tumour cell differentiation. We conclude that GDNF may be important in pancreatic cancer proliferation and metastasis, especially in patients with perineural invasion. Strongly positive expression of GDNF may be an indication for early intensified radiotherapy.RET expression in pancreatic cancer tissues may be a useful prognostic marker.

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The role of glial cell line‐derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells

Abstract: The enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences invasion and adhesion to ECM proteins by pancreatic cancer cells.

Cited by 43 publications

References 18 publications

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression

The Relationship between Over-expression of Glial Cell-derived Neurotrophic Factor and Its RET Receptor with Progression and Prognosis of Human Pancreatic Cancer

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