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A. Ochiai
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-055 - Fibroblast-Dependent Cancer Cell Invasion: Analysis of Cancer-Associated Fibroblasts That Remodel the Extracellular Matrix (ID 2633)
09:30 - 17:00 | Author(s): A. Ochiai
- Abstract
Background:
Cancer-associated fibroblasts (CAFs) communicate with cancer cells and play important roles in cancer invasion. We previously reported that local invasion of cancer cells was frequently observed in lung adenocarcinoma patients with podoplanin(PDPN)-expressing CAFs. However, the underlying mechanisms of this phenomenon have remained unclear.
Methods:
We established a novel collagen invasion assay model in which cancer cells and CAFs were co-cultured; we analyzed the mechanisms governing how cancer cell invasion was promoted by PDPN(+)CAFs.
Results:
By observing the dynamic movement of both CAFs and cancer cells in the collagen matrix, we found that PDPN(+)CAFs invaded the matrix to a greater extent, with more cancer cells invading within the “tracks” created by the CAFs, compared with control CAFs. The knockdown of PDPN in CAFs decreased the invasion of both the CAFs and the cancer cells. PDPN(+)CAFs displayed a higher RhoA activity, and treatment with a ROCK inhibitor cancelled the increased invasion ability of PDPN(+)CAFs and subsequently decreased the number of invaded cancer cells. After intravenous injection in the mouse tail vein, PDPN(+)CAFs invaded and promoted cancer cell invasion into the lung parenchyma, compared with control CAFs. Among the patients with lung adenocarcinoma, we observed some cases with PDPN(+)CAFs at the invasive front of the tumor. These cases predominantly exhibited pleural invasion of cancer cells, known as pathological invasiveness.
Conclusion:
Our results indicated that PDPN(+)CAFs were tumor-promoting CAFs that lead and enhance the local invasion of cancer cells, suggesting that the invasion activity of CAFs themselves could be rate-determining for cancer cell invasion. For analysis of fibroblast-dependent cancer cell invasion, we established single-cell derived clones from primarily cultured CAFs and conduct further investigation.
