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Article: Dedifferentiation of stromal smooth muscle as a factor in prostate carcinogenesis

TitleDedifferentiation of stromal smooth muscle as a factor in prostate carcinogenesis
Authors
Issue Date2002
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/DIF
Citation
Differentiation, 2002, v. 70 n. 9-10, p. 633-645 How to Cite?
AbstractWe had earlier established an animal model of prostate carcinogenesis using a combination of testosterone (T) and 17β-estradiol benzoate (E2) on Noble rats (Wang and Wong, 1998). In the present study we examined the changes in a number of smooth muscle differentiation markers including smooth muscle α-actin and myosin, vinculin, desmin, laminin and vimentin as well as changes in fine structure by electron microscopy. Our immunohistochemical (IHC) studies revealed that smooth muscle cells (SMCs) subjacent to dysplastic (precancerous) sites and carcinoma usually exhibited a preferential loss of myosin, desmin and laminin. However, the expression of α-actin and vinculin appeared to be more persistent in most dysplastic or neoplastic sites. The study reaffirmed our earlier observation that there was a concurrent dedifferentiation of surrounding SMCs during the development and progression of prostate carcinogenesis. The structural study revealed that SMC subjacent to epithelial dysplasia displayed a spectrum of derangements. These included the loosening of muscular layers with SMC characterized by their highly irregular external contours with numerous spine-like cytoplasmic projections. There was also a reduction in density of myofilaments and presence of many enlarged caveolae in muscle cells. Additionally, focal discontinuity or disruptions of muscular layer were often observed together with an increase in abundance of fibrous connective tissue. Moreover, the amount of smooth muscle appeared to be inversely correlated with the histologic grade of prostate tumors. In most instances, SMCs were totally absent in the moderately or poorly differentiated tumors and in metastatic tumors in the lung and the small intestine. Stromal muscular deformity was associated with concurrent changes in epithelial cells. Dysplastic epithelial cells were characterized by a reduction in abundance of secretory organelles such as reduction in size of Golgi apparatus, paucity of granular endoplasmic reticulum and secretory vesicles. The nuclei showed typical deformity characterized by deep nuclear membrane foldings. The basal lamina of dysplastic or tumor cells was present although focal structural abnormalities such as reduplication, disruption and smearing were sometimes observed. The present data indicate that derangements of epithelial cells during prostate carcinogenesis are associated with a reduction or dedifferentiation of stromal SMCs. Our results lend support to the hypothesis that transformed epithelium is incapable of maintaining normal differentiation of adjacent muscle. In turn, abnormal stromal, resulting from dedifferentiation or reduction of SMC, may lead to loss of stromal control over epithelial proliferation and differentiation. Consequently, a loss of differentiation in both epithelium and stromal SMCs may be critically involved in hormone-induced prostate carcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/67564
ISSN
2015 Impact Factor: 2.461
2015 SCImago Journal Rankings: 1.747
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, YCen_HK
dc.contributor.authorTam, NNCen_HK
dc.date.accessioned2010-09-06T05:56:15Z-
dc.date.available2010-09-06T05:56:15Z-
dc.date.issued2002en_HK
dc.identifier.citationDifferentiation, 2002, v. 70 n. 9-10, p. 633-645en_HK
dc.identifier.issn0301-4681en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67564-
dc.description.abstractWe had earlier established an animal model of prostate carcinogenesis using a combination of testosterone (T) and 17β-estradiol benzoate (E2) on Noble rats (Wang and Wong, 1998). In the present study we examined the changes in a number of smooth muscle differentiation markers including smooth muscle α-actin and myosin, vinculin, desmin, laminin and vimentin as well as changes in fine structure by electron microscopy. Our immunohistochemical (IHC) studies revealed that smooth muscle cells (SMCs) subjacent to dysplastic (precancerous) sites and carcinoma usually exhibited a preferential loss of myosin, desmin and laminin. However, the expression of α-actin and vinculin appeared to be more persistent in most dysplastic or neoplastic sites. The study reaffirmed our earlier observation that there was a concurrent dedifferentiation of surrounding SMCs during the development and progression of prostate carcinogenesis. The structural study revealed that SMC subjacent to epithelial dysplasia displayed a spectrum of derangements. These included the loosening of muscular layers with SMC characterized by their highly irregular external contours with numerous spine-like cytoplasmic projections. There was also a reduction in density of myofilaments and presence of many enlarged caveolae in muscle cells. Additionally, focal discontinuity or disruptions of muscular layer were often observed together with an increase in abundance of fibrous connective tissue. Moreover, the amount of smooth muscle appeared to be inversely correlated with the histologic grade of prostate tumors. In most instances, SMCs were totally absent in the moderately or poorly differentiated tumors and in metastatic tumors in the lung and the small intestine. Stromal muscular deformity was associated with concurrent changes in epithelial cells. Dysplastic epithelial cells were characterized by a reduction in abundance of secretory organelles such as reduction in size of Golgi apparatus, paucity of granular endoplasmic reticulum and secretory vesicles. The nuclei showed typical deformity characterized by deep nuclear membrane foldings. The basal lamina of dysplastic or tumor cells was present although focal structural abnormalities such as reduplication, disruption and smearing were sometimes observed. The present data indicate that derangements of epithelial cells during prostate carcinogenesis are associated with a reduction or dedifferentiation of stromal SMCs. Our results lend support to the hypothesis that transformed epithelium is incapable of maintaining normal differentiation of adjacent muscle. In turn, abnormal stromal, resulting from dedifferentiation or reduction of SMC, may lead to loss of stromal control over epithelial proliferation and differentiation. Consequently, a loss of differentiation in both epithelium and stromal SMCs may be critically involved in hormone-induced prostate carcinogenesis.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/DIFen_HK
dc.relation.ispartofDifferentiationen_HK
dc.rightsDifferentiation. Copyright © Elsevier Ltd.en_HK
dc.subject.meshActins - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBiological Markersen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Transformation, Neoplastic - pathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMyocytes, Smooth Muscle - pathologyen_HK
dc.subject.meshProstatic Neoplasms - etiology - metabolism - pathologyen_HK
dc.subject.meshRatsen_HK
dc.subject.meshVinculin - metabolismen_HK
dc.titleDedifferentiation of stromal smooth muscle as a factor in prostate carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0301-4681&volume=70&spage=633&epage=645&date=2002&atitle=Dedifferentiation+of+stromal+smooth+muscle+as+a+factor+in+prostate+carcinogenesisen_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1046/j.1432-0436.2002.700916.xen_HK
dc.identifier.pmid12492504-
dc.identifier.scopuseid_2-s2.0-0036992806en_HK
dc.identifier.hkuros75559en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036992806&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue9-10en_HK
dc.identifier.spage633en_HK
dc.identifier.epage645en_HK
dc.identifier.isiWOS:000179946700016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridTam, NNC=7101712624en_HK

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