title: Structure and Function of a Prostate Cancer Dissemination-Permissive Extracellular Matrix.
abstract: Purpose:The poor prognosis of metastatic prostate cancer continues to present a major challenge in prostate cancer treatment. The tumor extracellular matrix (ECM) plays an important role in facilitating metastasis. Here, we investigated the structure and function of an ECM that facilitates prostate cancer metastasis by comparing orthotopic tumors that frequently metastasize to poorly metastatic subcutaneous tumors.Experimental Design:Both tumors were derived from a human prostate cancer PC3 cell line engineered to fluoresce under hypoxia. Second harmonic generation (SHG) microscopy was used to characterize collagen 1 (Col1) fiber patterns in the xenografts as well as in human samples. MRI was used to determine albumin-Gd-diethylenetriaminepenta-acetate (alb-GdDTPA) transport through the ECM using a saturation recovery MR method combined with fast T1SNAPSHOT-FLASH imaging. Cancer-associated fibroblasts (CAF) were also quantified in these tumors.Results:Significant structural and functional differences were identified in the prometastatic orthotopic tumor ECM compared to the less metastatic subcutaneous tumor ECM. The significantly higher number of CAFs in orthotopic tumors may explain the higher Col1 fiber volumes in these tumors.In vivo, alb-GdDTPA pooling was significantly elevated in metastatic orthotopic tumors, consistent with the increased Col1 fibers.Conclusions:Developing noninvasive MRI indices of macromolecular transport, together with characterization of Col1 fiber patterns and CAFs can assist in stratifying prostate cancers for aggressive treatments or active surveillance. These results highlight the role of CAFs in supporting or creating aggressive cancers, and the importance of depleting CAFs to prevent metastatic dissemination in prostate cancer.Clin Cancer Res; 23(9); 2245-54. ©2016 AACR.
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Marie-France
authors: MF
authors: Penet
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.
authors: Samata
authors: S
authors: Kakkad
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Arvind P
authors: AP
authors: Pathak
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.
authors: Balaji
authors: B
authors: Krishnamachary
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.
authors: Yelena
authors: Y
authors: Mironchik
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Venu
authors: V
authors: Raman
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland.
authors: Meiyappan
authors: M
authors: Solaiyappan
authors: In-Vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, John Hopkins University School of Medicine, Baltimore, Maryland. zaver@mri.jhu.edu.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Zaver M
authors: ZM
authors: Bhujwalla
mesh_terms: D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D005109:Extracellular Matrix / Q000648:ultrastructure*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D011379:Prognosis; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D059016:Tumor Microenvironment / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D024042:Collagen Type I