Abstract
Ovarian cancer is the most lethal gynaecologic malignancy in the United States, and advanced serous ovarian adenocarcinoma is responsible for most ovarian cancer deaths. However, the stroma-derived molecular determinants that modulate patient survival are yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumour samples and find that stromal microfibrillar-associated protein 5 (MFAP5) is a prognostic marker for poor survival. Further functional studies reveal that FAK/CREB/TNNC1 signalling pathways mediate the effect of MFAP5 on ovarian cancer cell motility and invasion potential. Targeting stromal MFAP5 using MFAP5-specific siRNA encapsulated in chitosan nanoparticles significantly decreases ovarian tumour growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Adenocarcinoma / metabolism
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Calcium / metabolism
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Cell Line, Tumor
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Cell Movement
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Contractile Proteins / metabolism*
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Female
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Focal Adhesion Protein-Tyrosine Kinases / metabolism*
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Glycoproteins / metabolism*
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Humans
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Immunohistochemistry
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Intercellular Signaling Peptides and Proteins
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Neoplasm Metastasis
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Ovarian Neoplasms / metabolism*
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Prognosis
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RNA, Small Interfering / metabolism
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Signal Transduction*
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Stromal Cells / cytology
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Treatment Outcome
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Troponin C / metabolism*
Substances
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Actins
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CREB1 protein, human
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Contractile Proteins
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Cyclic AMP Response Element-Binding Protein
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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MFAP5 protein, human
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RNA, Small Interfering
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Troponin C
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Focal Adhesion Protein-Tyrosine Kinases
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Calcium