Back to Search
Start Over
Podoplanin Expression Identified in Stromal Fibroblasts as a Favorable Prognostic Marker in Patients with Colorectal Carcinoma
- Source :
- Oncology. 77:53-62
- Publication Year :
- 2009
- Publisher :
- S. Karger AG, 2009.
-
Abstract
- Objective: The microenvironment of cancer plays a critical role in its progression. However, the molecular features of cancer-associated fibroblasts (CAFs) are less well understood than those of cancer cells. We investigated the clinicopathological significance of podoplanin expression in stromal fibroblasts in patients with colorectal cancer (CRC). Methods: We selected podoplanin as an upregulated marker in CAF from a DNA microarray experiment. Consequently, podoplanin was identified as an upregulated gene. Immunohistochemical podoplanin expression was investigated at the National Cancer Center Hospital, Tokyo, Japan, in 120 patients with advanced CRC, and its clinicopathological significance was examined. The biological function of podoplanin expression was also assessed by a coculture invasion assay with CRC cell lines such as HCT116 and HCT15. Results: Podoplanin expression was exclusively confined to stromal fibroblasts and absent in tumor cells. Podoplanin is absent in normal stroma except for lymphatic vessels. Staining was considered positive when over 30% of the cancer stroma was stained. Positive podoplanin expression was significantly correlated with a more distal tumor localization (p = 0.013) and a shallower depth of tumor invasion (p = 0.011). Univariate analysis revealed that negative podoplanin expression in stromal fibroblasts was significantly associated with reduced disease-specific survival (p = 0.0017) and disease-free survival (p < 0.0001). Multivariate analysis revealed that negative podoplanin expression (p = 0.016) and lymph node metastasis (p = 0.027) were significantly associated with disease-free survival. CRC cell invasion was augmented by co-culture with CAFs that were treated with siRNA for podoplanin. Conclusions: Our results suggest that a positive podoplanin expression in stromal fibroblasts could have a protective role against CRC cell invasion and is a significant indicator of a good prognosis in patients with advanced CRC, supported by biological analysis showing that podoplanin expression in CAFs is associated with decreased CRC cell invasion.
- Subjects :
- Adult
Male
Cancer Research
Pathology
medicine.medical_specialty
Colorectal cancer
Blotting, Western
Adenocarcinoma
Immunoenzyme Techniques
Stroma
Biomarkers, Tumor
medicine
Humans
Neoplasm Invasiveness
RNA, Small Interfering
Fibroblast
Survival rate
Cells, Cultured
Aged
Neoplasm Staging
Aged, 80 and over
Membrane Glycoproteins
business.industry
Cancer
Anatomical pathology
General Medicine
Fibroblasts
Middle Aged
Prognosis
medicine.disease
Survival Rate
Drug Combinations
medicine.anatomical_structure
Oncology
Podoplanin
Culture Media, Conditioned
Lymphatic Metastasis
Cancer research
Immunohistochemistry
Female
Proteoglycans
Collagen
Laminin
Stromal Cells
Colorectal Neoplasms
business
Subjects
Details
- ISSN :
- 14230232 and 00302414
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Oncology
- Accession number :
- edsair.doi.dedup.....75496f3a019bbbbaa11ce9c5765232ae