Notch and TGF-beta/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma
Zhang, Jie; Wang, Y; Li, Dan; Jing, S
| HERO ID | 2454001 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Notch and TGF-beta/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma |
| Authors | Zhang, Jie; Wang, Y; Li, Dan; Jing, S |
| Journal | Tumor Biology |
| Volume | 35 |
| Issue | 1 |
| Page Numbers | 379-385 |
| Abstract | Accumulating evidence suggests that cancer-associated stromal fibroblasts (CAFs) contribute to tumor growth by actively communicating with cancer cells. Our aim was to identify the signaling pathways that are involved in tumor-stromal cell interactions in human papillary thyroid carcinoma (PTC). Immunohistochemical analyses were performed with 127 archived formalin-fixed and paraffin-embedded thyroid tissue samples that included 70 cases of PTC, 35 cases of nodular goiter (NG), and 22 cases of normal thyroid tissues. The results showed that the expression levels of Notch1, transforming growth factor beta (TGF-beta 1), and p-Smad3 in PTC cells and alpha-smooth muscle actin (alpha-SMA) in the stroma of PTC were all significantly higher than in NG and normal thyroid tissues. Further analysis showed that in PTC, higher expression levels of Notch1 and TGF-beta 1 were closely related with lymph node metastasis (P < 0.05), whereas for alpha-SMA and p-Smad3, the percent expression increased significantly with advanced tumor stages (P < 0.05). Correlation analysis revealed that TGF-beta 1 expression increased with increased Notch1 and p-Smad3 levels in PTC cells (P < 0.05). Moreover, a significant correlation was found between higher TGF-beta 1 expression in PTC cells and increased alpha-SMA levels in the fibroblasts surrounding the cancer cells (P < 0.05). We identified TGF-beta 1 as an important factor from PTC cells that act in a paracrine manner to influence the activation of stromal fibroblasts. These data suggest that the activation of Notch and TGF-beta/Smad3 pathways in cancer cells influence tumor growth. Moreover, cancer cell-derived-TGF-beta ligands also affect stromal cells in a paracrine fashion and enhance tumor growth. |
| Doi | 10.1007/s13277-013-1053-z |
| Pmid | 23918305 |
| Wosid | WOS:000331091000049 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Papillary thyroid carcinoma; Cancer-associated fibroblasts; Notch; TGF-beta/Smad3; alpha-SMA |