Prostate Stroma: Physiology

Farnsworth, Wells E.

doi:10.1002/(sici)1097-0045(19990101)38:1<60::aid-pros8>3.0.co;2-3

Cited by 70 publications

(31 citation statements)

References 98 publications

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“…The elastic fibres and membranes were observed mainly in large interlobular septa, where they were intermingled with [5]. In the rat prostate, the elastic fibres in this area were thin and inconspicuous as was described [3].…”

Section: Discussionmentioning

confidence: 70%

Immunohistochemical Localization of Elastic System Fibres in the Canine Prostate

Marettová

2017

Folia Veterinaria

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Section: Discussionmentioning

confidence: 70%

Immunohistochemical Localization of Elastic System Fibres in the Canine Prostate

Marettová

2017

Folia Veterinaria

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“…These factors were chosen because of their reported expression in PC tissues, including the epithelium and stroma. 26 Both TGF-␤1 (Fig. 5, lane 2) and TNF-␣, lane 5) stimulated pro-MMP-9 expression in 32 PC cells.…”

Section: Effect Of Growth Factors and Ecm Components On Pro-mmp-9 Expmentioning

confidence: 88%

“…The prostate tumor stroma contains smooth muscle cells, which are thought to provide paracrine signals to PC cells and to contribute to tumor progression. 26 Indeed, previous studies demonstrated the influence of the prostate stroma on the epithelial phenotype likely to be mediated by the production of growth factors by the prostate stroma. 18 -20 Our data indicate that porcine BrSM cells induce pro-MMP-9 expression in PC cells and, thus, may also play a role in ECM remodeling during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells

et al. 2001

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Tumor-stromal interactions have been suggested to be a critical factor in both tumor invasion and tumor metastasis. Here, we examined the role of tumor-stromal interactions using co-cultures of prostate cancer (PC) cells derived from primary and metastatic tumors with primary or immortalized stromal (fibroblast and smooth muscle) cells and their effect on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression. Co-cultures of PC and stromal cells showed enhanced levels of pro-MMP-9 and reduced levels of TIMP-1 and TIMP-2. Whereas enhanced expression of pro-MMP-9 occurred in PC cells, the TIMPs were down-regulated in stromal cells. Induction of pro-MMP-9 and reduction of TIMP expression did not require cell-cell contact and were mediated by a soluble factor(s) present in the conditioned medium of the effector cell. Collagen I is a potent inducer of pro-MMP-9 in PC cells. Consistently, preliminary characterization of the soluble factor in the fibroblast conditioned medium revealed m.w. of approximately 100 to 250 kDa, and its effect on pro-MMP-9 expression was partly inhibited by an anti-␣2 integrin antibody, a major collagen I receptor. Expression of pro-MMP-9 protein and mRNA was also induced in metastatic PC-3 cells grown in human fetal bone implants in SCID mice. Metastasis formation is the hallmark of cancer and the major cause of mortality. Tumor metastasis involves extensive interactions of the invasive cancer cells with host stromal components, and such interactions promote degradation of the extracellular matrix (ECM) by specialized proteolytic enzymes produced by both the cancer and the stromal cells. These interactions are likely to occur in both primary and metastatic sites. Among the proteases involve in ECM degradation during tumor invasion, the family of matrix metalloproteinases (MMPs) has been shown to play a key role due to their ability to degrade a variety of ECM and basement membrane components. 1-3 All MMPs are specifically inhibited by the tissue inhibitors of matrix metalloproteinases (TIMPs), a family of proteins that presently includes TIMP-1, TIMP-2, TIMP-3 and TIMP-4. 4 The TIMPs inhibit all active MMPs, albeit with different affinities, by binding to the active site of the enzyme. Consequently, the balance between MMP and TIMP levels has been considered to be a critical determinant of the net proteolytic activity at any given time. 5 In tumor tissues, differential expression of MMPs and TIMPs in the tumor and stromal cells may tilt the balance and thus influence MMP activity and eventually tumor cell invasion. However, little is known about the regulation of MMP and TIMP levels in tumor and stromal tissues.Prostate cancer (PC) is the most common cancer and the second leading cause of cancer death in American men. 6 Metastatic PC cells invade initially into the prostate stroma, where they intimately interact with stromal cells and ECM components. Eventually, PC cells metastasize preferentially to bone tissues, where they interact with bone stromal cell...

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“…New approaches are badly needed to treat prostate cancer metastasis. One such approach is to consider prostate cancer as an organ consisting of both tumor epithelium and supporting prostate stroma when in the primary, or bone stroma after metastasis to bone, 16,17 and associated neovasculature. 18 While the importance of tumor angiogenesis is well appreciated and the concept of cotargeting both tumor and neovasculature is well accepted, there has been little progress in cotargeting tumor and its associated stroma in experimental and clinical settings.…”

mentioning

confidence: 99%

Cotargeting tumor and stroma in a novel chimeric tumor model involving the growth of both human prostate cancer and bone stromal cells

Hsieh

Gardner

et al. 2003

Cancer Gene Ther

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Stromal-epithelial interaction contributes to local prostate tumor growth, androgen-independent progression and distant metastasis. We have established in vitro coculture and in vivo chimeric tumor models to evaluate the roles of stromal cells isolated from either osteosarcoma or normal bone, a site where prostate cancer cells frequently metastasize, in contributing to the growth and survival of human prostate cancer cells. We have evaluated extensively the effects of toxic gene therapy using luciferase-tagged chimeric human prostate cancer models both in vitro and in vivo. In the in vitro cocultured cell model, we assessed cancer cell growth and residual cellular proteins after targeting either prostate cancer epithelial cells alone or both prostate cancer and bone stromal cells. In the in vivo animal model, we measured tumor volume and serum prostate-specific antigen (PSA) in mice bearing chimeric prostate tumors comprised of human prostate tumor cells and normal bone stromal cells. Our results demonstrated that: (1) The rate of human prostate cancer cell growth in vitro is accelerated by coculturing with human and rat osteosarcoma or normal mouse bone marrow stromal cell lines. No growth stimulation was noted when cocultured with a human prostate epithelial cell line. (2) Disabling the growth of normal bone stromal cells using transgenic targeting with a bystander gene, herpes simplex virus thymidine kinase (hsv-TK), plus the pro-drug ganciclovir (GCV) or acyclovir markedly depressed the growth of cocultured human prostate cancer cells in vitro and human prostate cancer-mouse normal bone stroma chimeric tumors in vivo. (3) By cotargeting both human prostate cancer and normal mouse bone stromal cells in vitro with an adenoviral construct, Ad-hOC-TK (a replication-defective Ad5 vector with the bystander transgene hsv-TK under the control of a human osteocalcin (hOC) promoter) plus GCV 4 , we observed greater inhibition of tumor cell growth than by targeting a single cell compartment with Ad-PSA-TK (a vector construct similar to Ad-hOC-TK except that the transgene expression is under regulation by a full-length human PSA promoter). These results, taken together, established a basic principle that cotargeting both tumor and its supporting stroma is more efficacious than targeting a single cell compartment in the treatment of human prostate cancer bone metastasis. This principle can be applied to other clinical conditions of cancer growth where stroma contribute to the overall growth and survival potential of the cancer.

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Prostate Stroma: Physiology

Cited by 70 publications

References 98 publications

Immunohistochemical Localization of Elastic System Fibres in the Canine Prostate

Immunohistochemical Localization of Elastic System Fibres in the Canine Prostate

Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells

Cotargeting tumor and stroma in a novel chimeric tumor model involving the growth of both human prostate cancer and bone stromal cells

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