Microenvironment Elements Involved in the Development of Pancreatic Cancer Tumor

Abstract

Introduction. In spite of intensive research during many years, pancreatic adenocarcinoma remains one of the deadliest cancers. The surgical intervention remains main possibility of treatment because chemotherapy and radiotherapy has a minimal impact on long-term survival. We are still looking for the weak points of this devastating disease. Materials and Methods. Pancreatic tumor tissue samples were collected from 36 patients. Immunohistochemistry staining was used to evaluate expression of growth factors and immune infiltrates. Activity of MMP2 and MMP9 was assessed by gelatin zymography on 7.5% SDS-PAGE gel with 0.1% gelatin. Results. All growth factors were strongly expressed in pancreatic tumor tissue. We found that level of expression of c-Met receptor was higher for G3 tumors than for G2 tumors. Also we found that active MMP2 was present at all stages of tumor while active MMP9 just at more advanced tumors. Abundant immune cells infiltration was distinctive for tumor tissue, especially macrophages were infiltrating tumor tissue. We found that amount of macrophages was associated with lymph nodes metastases. Conclusion. In our research we demonstrated that among many factors influencing tumor microenvironment c-Met receptor, infiltrating macrophages and MMP2 have significant influence on development and invasion of pancreatic cancer.

High c‐Met expression in stage I–II pancreatic adenocarcinoma: proposal for an immunostaining scoring method and correlation with poor prognosis

“…In this study, we have shown that high c‐Met expression, assessed with the simplified c‐Met score, is an independent prognostic marker of poor survival in patients with resected stage I–II PDAC. Our results are consistent with previously published data, and show that, with this simple and reproducible scoring method, c‐Met expression is an independent prognostic factor for both DFS and OS in multivariate analysis (Table ) . Discrepancies in the prognostic value of c‐Met expression in PDAC in previous reports could be related to the type of immunoassay method and the use of less discriminant scoring methods for quantifying c‐Met expression.…”

SU11274 suppresses proliferation and motility of pancreatic cancer cells

“…Following treatment with 30 µM SU11274, cell motility was suppressed to 1.0±0.3% in MIA-Paca2 cells (P<0.05) and 14.7±3.5% in PK-45H cells (P<0.05) of the level of cells treated with 0 µM SU11274, respectively. Discussion c-Met expression has been identified in pancreatic cancer specimens (11). In the present study, immunostaining detected no c-Met expression at the protein level in normal pancreatic tissues.…”

Elastography Can Map the Local Inverse Relationship between Shear Modulus and Drug Delivery within the Pancreatic Ductal Adenocarcinoma Microenvironment

“…Consequently, developing therapies for either treating the disease or allowing more patients to qualify for surgery is an area of active research (4,5). High tissue pressure can impede the delivery of therapeutic agents and encourage tumor progression (40,41). Tissue pressure is difficult to measure with currently available invasive pressure catheters.…”