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Published on: September 23, 2014
Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas
H Koizumi1, M Morita, S Mikami
1Second Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan. hiro@marianna-u.ac.jp
Abstract:
The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-beta, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved in the growth of certain non-neuronal carcinomas.
Insights
TrkA receptor tyrosine kinase is expressed in various non-neuronal human cancers. Its interaction with nerve growth factor may drive the growth of certain carcinomas, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Trk receptors, including TrkA, are crucial for neural tissue development and maintenance.
- Trk receptors are also expressed in various normal non-neuronal human tissues in a cell-specific manner.
Purpose of the Study:
- To investigate the expression patterns of TrkA in non-neuronal invasive carcinomas across 15 human tissues.
- To explore the potential role of nerve growth factor-beta (NGF) and TrkA interactions in carcinoma growth.
Main Methods:
- Immunohistochemical analysis of TrkA expression in 337 non-neuronal invasive carcinomas.
- Immunostaining for NGF-beta in esophageal and breast carcinomas.
Main Results:
- TrkA immunoreactivity was observed in 70% of the analyzed tumors (39% strong, 30% moderate).
- Esophageal and thyroid carcinomas showed high TrkA levels, while gastric and colon cancers had low levels.
- TrkA was found in carcinomas from both TrkA-positive (esophagus, breast, lung, uterus) and TrkA-negative (thyroid, liver, ovary) normal tissues.
- NGF-beta was detected in stromal fibroblasts and some tumor cells in esophageal and breast carcinomas.
Conclusions:
- TrkA is expressed in a significant proportion of non-neuronal human carcinomas.
- Paracrine/autocrine regulation involving stromal/tumoral NGF and tumoral TrkA may contribute to the growth of certain non-neuronal carcinomas.
- These findings suggest TrkA as a potential therapeutic target for specific cancers.
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