title: Impact of stroma on the growth, microcirculation, and metabolism of experimental prostate tumors.
abstract: In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and (1)H magnetic resonance spectroscopy ([(1)H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.
authors.affiliation: Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Zechmann
authors.forename: Eva C
authors.initials: EC
authors.lastname: Woenne
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brix
authors.forename: Nicole
authors.initials: N
authors.lastname: Radzwill
authors.forename: Martin
authors.initials: M
authors.lastname: Ilg
authors.forename: Peter
authors.initials: P
authors.lastname: Bachert
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
authors.forename: Stefan
authors.initials: S
authors.lastname: Kirsch
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Kauczor
authors.forename: Stefan
authors.initials: S
authors.lastname: Delorme
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017154:Stromal Cells / Q000502:physiology*