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2018 ; 20
(4
): 387-400
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Nephronectin is Correlated with Poor Prognosis in Breast Cancer and Promotes
Metastasis via its Integrin-Binding Motifs
#MMPMID29539586
Steigedal TS
; Toraskar J
; Redvers RP
; Valla M
; Magnussen SN
; Bofin AM
; Opdahl S
; Lundgren S
; Eckhardt BL
; Lamar JM
; Doherty J
; Hynes RO
; Anderson RL
; Svineng G
Neoplasia
2018[Apr]; 20
(4
): 387-400
PMID29539586
show ga
Most cancer patients with solid tumors who succumb to their illness die of
metastatic disease. While early detection and improved treatment have led to
reduced mortality, even for those with metastatic cancer, some patients still
respond poorly to treatment. Understanding the mechanisms of metastasis is
important to improve prognostication, to stratify patients for treatment, and to
identify new targets for therapy. We have shown previously that expression of
nephronectin (NPNT) is correlated with metastatic propensity in breast cancer
cell lines. In the present study, we provide a comprehensive analysis of the
expression pattern and distribution of NPNT in breast cancer tissue from 842
patients by immunohistochemical staining of tissue microarrays from a historic
cohort. Several patterns of NPNT staining were observed. An association between
granular cytoplasmic staining (in <10% of tumor cells) and poor prognosis was
found. We suggest that granular cytoplasmic staining may represent NPNT-positive
exosomes. We found that NPNT promotes adhesion and anchorage-independent growth
via its integrin-binding and enhancer motifs and that enforced expression in
breast tumor cells promotes their colonization of the lungs. We propose that NPNT
may be a novel prognostic marker in a subgroup of breast cancer patients.