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Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.


ABSTRACT:

Background

Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.

Methods

Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+?CAFs and PDPN- CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs.

Results

PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P?=?0.0461), vascular invasion (P?=?0.0101), tumor size ? 3 cm (P?=?0.0038), histological grade (P?=?0.0344), Union for International Cancer Control classification T stage (P?=?0.029), and shorter survival time (P?ConclusionsPDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.

SUBMITTER: Shindo K 

PROVIDER: S-EPMC3916072 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.

Shindo Koji K   Aishima Shinichi S   Ohuchida Kenoki K   Fujiwara Kenji K   Fujino Minoru M   Mizuuchi Yusuke Y   Hattori Masami M   Mizumoto Kazuhiro K   Tanaka Masao M   Oda Yoshinao Y  

Molecular cancer 20131220 1


<h4>Background</h4>Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.<h4>Methods</h4>Expression of PDPN in pancreatic IDCs wa  ...[more]

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