Therapeutical efficacy of tyrosine kinase inhibitors in oncology is well known. The transducing receptors for neurotrophins, including TrKA for Nerve Growth Factor (NGF), have a tyrosine kinase activity and very recently data have been reported suggesting that targeting NGF receptors in cancer cells is a promising therapeutical approach. However, these data are few and fragmentary, and the question of the importance of NGF/TrKA in oncology is still well open. In a previous research (I), we have shown that NGF plays a key role in the proliferation of a cell line of rhabdomyosarcoma. Starting from these preliminary data,. we amplified our results studying the biological role of NGF and its receptors in several lines of human neoplasms, in particular sarcomas from smooth and striated muscle, prostatic and lung cancers, and leukemias. These lines were analyzed for the expression of NGF and is receptors (PCR, Western Blotting, ICC), for release of NGF into the conditioned medium (ELISA and biological assay with PCl2 cells), for proliferation (timidine tritiate assay and cell counts), for apoptosis (Annexin V assay). Our results show that all the lines express NGF and its receptors and actively release NGF into the conditioned medium. Addition of NGF into the medium of these neoplastic cell lines did not induce any modification in their proliferation and apoptosis, neither induced differentiation. However the specific block of TrKA, the transducing receptor for NGF, by tyrphostin AG879 induced a dramatic dose-dependent decrease in neoplastic proliferation and in most of the lines induced an increase in apoptosis. These data indicate that, at least in vitro, neoplastic cell lines may use NGF in autocrine manner and that NGF/TrKA binding can be a key step in the proliferation of these cells. Furthermore, the present data strongly suggest a TrKA involvement in the proliferation of neoplastic cells and extend the role of NGF, which could be important in the clinical management of these conditions.
ROLE OF NERVE GROWTH FACTOR (NGF") AND ITS TRANSDUCING REGEPTOR TrKA IN SOME NEOPLASTIC CELL LINES
R. BRUNO
2002-01-01
Abstract
Therapeutical efficacy of tyrosine kinase inhibitors in oncology is well known. The transducing receptors for neurotrophins, including TrKA for Nerve Growth Factor (NGF), have a tyrosine kinase activity and very recently data have been reported suggesting that targeting NGF receptors in cancer cells is a promising therapeutical approach. However, these data are few and fragmentary, and the question of the importance of NGF/TrKA in oncology is still well open. In a previous research (I), we have shown that NGF plays a key role in the proliferation of a cell line of rhabdomyosarcoma. Starting from these preliminary data,. we amplified our results studying the biological role of NGF and its receptors in several lines of human neoplasms, in particular sarcomas from smooth and striated muscle, prostatic and lung cancers, and leukemias. These lines were analyzed for the expression of NGF and is receptors (PCR, Western Blotting, ICC), for release of NGF into the conditioned medium (ELISA and biological assay with PCl2 cells), for proliferation (timidine tritiate assay and cell counts), for apoptosis (Annexin V assay). Our results show that all the lines express NGF and its receptors and actively release NGF into the conditioned medium. Addition of NGF into the medium of these neoplastic cell lines did not induce any modification in their proliferation and apoptosis, neither induced differentiation. However the specific block of TrKA, the transducing receptor for NGF, by tyrphostin AG879 induced a dramatic dose-dependent decrease in neoplastic proliferation and in most of the lines induced an increase in apoptosis. These data indicate that, at least in vitro, neoplastic cell lines may use NGF in autocrine manner and that NGF/TrKA binding can be a key step in the proliferation of these cells. Furthermore, the present data strongly suggest a TrKA involvement in the proliferation of neoplastic cells and extend the role of NGF, which could be important in the clinical management of these conditions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
