Altered Expression of Neurotensin Receptors Is Associated with the Differentiation State of Prostate Cancer

TY - JOUR

T1 - Altered Expression of Neurotensin Receptors Is Associated with the Differentiation State of Prostate Cancer

AU - Swift, Stephanie L.

AU - Burns, Julie E.

AU - Maitland, Norman J.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - In prostate cancer, traditional treatments such as androgen response manipulation often provide only temporary resolution of disease, with emergence of a more aggressive, androgen-independent tumor following initial therapy. To treat recurrent disease, cell surface proteins that are specifically overexpressed on malignant cells may be useful for generating targeted therapeutics. Recent evidence suggests that neurotensin receptors (NTR) are recruited in advanced prostate cancer as an alternative growth pathway in the absence of androgens. In this study, we assessed the potential use of these receptors as targets by analyzing NTR expression patterns in human prostate cell lines and primary prostate tumor cell cultures derived from patient samples. In primary tumor cell cultures, NTR1 was upregulated in cells with a basal phenotype (cytokeratin 1/5/10/14(+)), whereas NTR2 and NTR3 were upregulated in cells with luminal phenotype (cytokeratin 18(+)). Similar patterns of NTR expression occurred in benign prostate tissue sections, implicating differentiation state as a basis for the differences observed in tumor cell lines. Our findings support the use of NTRs as tools for therapeutic targeting in prostate cancers composed of both poorly differentiated and/or well-differentiated cells. Cancer Res; 70(1); 347-56. (C) 2010 AACR.

AB - In prostate cancer, traditional treatments such as androgen response manipulation often provide only temporary resolution of disease, with emergence of a more aggressive, androgen-independent tumor following initial therapy. To treat recurrent disease, cell surface proteins that are specifically overexpressed on malignant cells may be useful for generating targeted therapeutics. Recent evidence suggests that neurotensin receptors (NTR) are recruited in advanced prostate cancer as an alternative growth pathway in the absence of androgens. In this study, we assessed the potential use of these receptors as targets by analyzing NTR expression patterns in human prostate cell lines and primary prostate tumor cell cultures derived from patient samples. In primary tumor cell cultures, NTR1 was upregulated in cells with a basal phenotype (cytokeratin 1/5/10/14(+)), whereas NTR2 and NTR3 were upregulated in cells with luminal phenotype (cytokeratin 18(+)). Similar patterns of NTR expression occurred in benign prostate tissue sections, implicating differentiation state as a basis for the differences observed in tumor cell lines. Our findings support the use of NTRs as tools for therapeutic targeting in prostate cancers composed of both poorly differentiated and/or well-differentiated cells. Cancer Res; 70(1); 347-56. (C) 2010 AACR.

KW - CENTRAL-NERVOUS-SYSTEM

KW - CELL-LINES

KW - VARIANT ISOFORM

KW - CARCINOMA

KW - IDENTIFICATION

KW - BASAL

KW - INTERNALIZATION

KW - TRAFFICKING

KW - BINDING

KW - CLONING

UR - http://www.scopus.com/inward/record.url?scp=75149164771&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-1252

DO - 10.1158/0008-5472.CAN-09-1252

M3 - Article

C2 - 20048080

SN - 0008-5472

VL - 70

SP - 347

EP - 356

JO - Cancer research

JF - Cancer research

IS - 1

ER -