Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies

Yuan Li1, Janine A Burns1, Carol A Cheney1, Ningyan Zhang1, Salvatore Vitelli1, Fubao Wang1, Andrew Bett2, Michael Chastain2, Laurent P Audoly1, Zhi-Qiang Zhang1,31Department of Biologics Research, 2Department of Vaccine Research, Merck Research Laboratories, West Point, PA, USA; 3Clinical Developme...

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Autores principales:	Yuan Li, Janine A Burns, Carol A Cheney, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/beeff8bff40a4e49a92c0583a2605216
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spelling	oai:doaj.org-article:beeff8bff40a4e49a92c0583a26052162021-12-02T01:12:26ZDistinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies1177-54751177-5491https://doaj.org/article/beeff8bff40a4e49a92c0583a26052162010-06-01T00:00:00Zhttp://www.dovepress.com/distinct-expression-profiles-of-notch-1-protein-in-human-solid-tumors--a4586https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Yuan Li1, Janine A Burns1, Carol A Cheney1, Ningyan Zhang1, Salvatore Vitelli1, Fubao Wang1, Andrew Bett2, Michael Chastain2, Laurent P Audoly1, Zhi-Qiang Zhang1,31Department of Biologics Research, 2Department of Vaccine Research, Merck Research Laboratories, West Point, PA, USA; 3Clinical Development Laboratory, Merck Research Laboratories, Rahway, NJ, USAAbstract: Biological therapies, such as monoclonal antibodies (mAbs) that target tumor-associated antigens have been considered an effective therapeutic approach in oncology. In considering Notch-1 receptor as a potential target, we performed immunohistochemistry on tissue microarrays to determine 1) whether the receptor is overexpressed in tumor cells as compared to their corresponding normal tissues and 2) the clinical significance of its expression levels in human breast, colorectal, lung and prostate cancers. We found that the expression of Notch-1 protein was overexpressed in primary colorectal adenocarcinoma and nonsmall cell lung carcinoma (NSCLC), but not in primary ductal breast carcinoma or prostate adenocarcinoma. Further analysis revealed that higher levels of Notch-1 protein expression were significantly associated with poorer differentiation of breast and prostate tumors. Strikingly, for NSCLC, the expression levels of Notch-1 protein were found to be inversely correlated with tumor differentiation and progression. For colorectal tumors, however, no correlation of Notch-1 protein expression was found with any tumor clinicopathological parameters, in spite of its overexpression in tumor cells. Our data demonstrated the complexity of Notch-1 protein expression in human solid tumors and further supported the notion that the roles of Notch-1 expression in tumorigenesis are highly context-dependent. The findings could provide the basis for development of distinct therapeutic strategies of Notch-1 mAbs for its applications in the treatment of suitable types of human cancers.Keywords: Notch-1, target therapy, tissue microarray, immunohistochemistry Yuan LiJanine A BurnsCarol A Cheneyet alDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2010, Iss default, Pp 163-171 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yuan Li Janine A Burns Carol A Cheney et al Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
description	Yuan Li1, Janine A Burns1, Carol A Cheney1, Ningyan Zhang1, Salvatore Vitelli1, Fubao Wang1, Andrew Bett2, Michael Chastain2, Laurent P Audoly1, Zhi-Qiang Zhang1,31Department of Biologics Research, 2Department of Vaccine Research, Merck Research Laboratories, West Point, PA, USA; 3Clinical Development Laboratory, Merck Research Laboratories, Rahway, NJ, USAAbstract: Biological therapies, such as monoclonal antibodies (mAbs) that target tumor-associated antigens have been considered an effective therapeutic approach in oncology. In considering Notch-1 receptor as a potential target, we performed immunohistochemistry on tissue microarrays to determine 1) whether the receptor is overexpressed in tumor cells as compared to their corresponding normal tissues and 2) the clinical significance of its expression levels in human breast, colorectal, lung and prostate cancers. We found that the expression of Notch-1 protein was overexpressed in primary colorectal adenocarcinoma and nonsmall cell lung carcinoma (NSCLC), but not in primary ductal breast carcinoma or prostate adenocarcinoma. Further analysis revealed that higher levels of Notch-1 protein expression were significantly associated with poorer differentiation of breast and prostate tumors. Strikingly, for NSCLC, the expression levels of Notch-1 protein were found to be inversely correlated with tumor differentiation and progression. For colorectal tumors, however, no correlation of Notch-1 protein expression was found with any tumor clinicopathological parameters, in spite of its overexpression in tumor cells. Our data demonstrated the complexity of Notch-1 protein expression in human solid tumors and further supported the notion that the roles of Notch-1 expression in tumorigenesis are highly context-dependent. The findings could provide the basis for development of distinct therapeutic strategies of Notch-1 mAbs for its applications in the treatment of suitable types of human cancers.Keywords: Notch-1, target therapy, tissue microarray, immunohistochemistry
format	article
author	Yuan Li Janine A Burns Carol A Cheney et al
author_facet	Yuan Li Janine A Burns Carol A Cheney et al
author_sort	Yuan Li
title	Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
title_short	Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
title_full	Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
title_fullStr	Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
title_full_unstemmed	Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies
title_sort	distinct expression profiles of notch-1 protein in human solid tumors: implications for development of targeted therapeutic monoclonal antibodies
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/beeff8bff40a4e49a92c0583a2605216
work_keys_str_mv	AT yuanli distinctexpressionprofilesofnotch1proteininhumansolidtumorsimplicationsfordevelopmentoftargetedtherapeuticmonoclonalantibodies AT janineaburns distinctexpressionprofilesofnotch1proteininhumansolidtumorsimplicationsfordevelopmentoftargetedtherapeuticmonoclonalantibodies AT carolacheney distinctexpressionprofilesofnotch1proteininhumansolidtumorsimplicationsfordevelopmentoftargetedtherapeuticmonoclonalantibodies AT etal distinctexpressionprofilesofnotch1proteininhumansolidtumorsimplicationsfordevelopmentoftargetedtherapeuticmonoclonalantibodies
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Distinct expression profiles of Notch-1 protein in human solid tumors: Implications for development of targeted therapeutic monoclonal antibodies

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