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Contribution of neurotensin and its high affinity receptor to the response of chemotherapy in ovarian cancer

Abstract : Ovarian cancer (OC) is the eighth most common cause of cancer death in female worldwide. Because OC has often no apparent symptoms at the early stages, the majority is diagnosed at the advanced stages. The combination of carboplatin plus paclitaxel, results in a complete response rate in 40-60 % of the cases. However, more than 90% patients relapse after 2 years, and in most cases, recurrent patients becomes incurable due to the chemoresistance. The complex of neurotensin (NTS) and its high affinity receptor 1 (NTSR1) has been shown to promote cancer progression in many type of cancer, via proliferation, survival, migration, invasion cellular effects, and neoangiogenesis. To date, the role of the complex NTS/NTSR1 in the platinum-based chemotherapy has not been considered. I studied whether NTS/NTSR1 inhibitors could enhance chemotherapy and the related mechanism. In a series of 46 patients, NTS and NTSR1 were detected in 72% and 74% of cases, respectively. Transcriptome analysis in a large series of high grade OC showed that NTSR1 expression was correlated with higher stages and with platinum resistance. We studied the contribution of NTS/NTSR1 pathway to chemotherapy by using two OC cell lines. In the presence of NTSR1 specific antagonist, SR 48692, OC cells or experimental tumors showed an enhanced response to carboplatin. SR 48692 decreased the efflux of carboplatin and increase the DNA damage induced by the platinum. Apoptosis was also enhanced in the presence of NTSR1 antagonist. These results strengthen our hypothesis that the blockade of NTS/NTSR1 pathway enhances the response to chemotherapy and potentially sensitizes tumor cells resistant to platinum.
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https://tel.archives-ouvertes.fr/tel-01771868
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Submitted on : Thursday, April 26, 2018 - 1:39:11 PM
Last modification on : Tuesday, October 20, 2020 - 11:33:05 AM

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  • HAL Id : tel-01771868, version 2

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Jin Liu. Contribution of neurotensin and its high affinity receptor to the response of chemotherapy in ovarian cancer. Tissues and Organs [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2017. English. ⟨NNT : 2017PA066080⟩. ⟨tel-01771868v2⟩

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