Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis.

Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Research Abstract Details 

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Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Abstract Text:

Wolfram Kleeberger,G Steven Bova,Matthew E Nielsen,Mehsati Herawi,Ai-Ying Chuang,Jonathan I Epstein,David M Berman,

The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread.

Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Publishing Authors By Initials

W Kleeberger,GS Bova,ME Nielsen,M Herawi,AY Chuang,JI Epstein,DM Berman,

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Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 9199-206

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Oct

YEAR: 2007

Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis.

AFFILIATION: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Country: United States

AGENCY: United States NCI

GRANT: P50 CA58236

ACRONYM: CA

MEDLINETA: Cancer Res

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