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A. Ochiai
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-001 - Cancer Cell Invasion Driven by Extracellular Matrix Remodeling is Dependent on the Properties of Cancer‑Associated Fibroblasts (ID 3891)
14:30 - 14:30 | Author(s): A. Ochiai
- Abstract
Background:
As one form of tumor invasion, cancer cells can invade the extracellular matrix (ECM) through tracks that have been physically remodeled by cancer-associated fibroblasts (CAFs). However, CAFs are a heterogeneous population with diverse matrix-remodeling capacities. The purpose of this study is to investigate how CAFs with various matrix-remodeling capacities influence cancer cell invasion.
Methods:
We established single-cell derived clones from 3 primary cultures of CAFs from lung adenocarcinoma patients (Case 1, 5 clones; Case 2, 5 clones; Case 3, 7 clones). Using a co-culture model, we evaluated the correlations between the number of invaded cancer cells and the remodeling areas generated by CAF clones in each case.
Results:
When A549 lung adenocarcinoma cells and CAF clones were co-cultured, both the numbers of invaded cancer cells and the remodeling areas generated by the CAF clones varied greatly. The number of invaded cancer cells was moderately and strongly correlated with the remodeling areas generated by each CAF clone originating from Cases 1 and 2 (R[2] value = 0.53 and 0.68, respectively), suggesting that the remodeling areas in the ECM may determine the number of invaded cancer cells. In contrast, the number of invaded cancer cells was not correlated with the remodeling areas generated by CAF clones originating from Case 3, suggesting that factors other than the remodeling areas might determine the number of invading cancer cells.
Conclusion:
These findings showed two types of fibroblast-dependent cancer cell invasion that are dependent on and independent of the remodeling areas generated by CAFs.
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P3.01-033 - Changes in the Tumor Microenvironment during Lymphatic Metastasis of Lung Squamous Cell Carcinoma (ID 6341)
14:30 - 14:30 | Author(s): A. Ochiai
- Abstract
Background:
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma.
Methods:
We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN Macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases.
Results:
The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of cancer cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (p<0.001). Moreover stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (p<0.001). Immunohistochemical study revealed that EGFR expression level and frequency of geminin positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (p<0.05). The number of stromal cells indicated by staining of CD34, CD204 and smooth muscle actin α in ILT and LN-Mic also was significantly lower than in PT and LN-Mac (p<0.05).
Conclusion:
In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of cancer cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.
