Laminin-1 and ?6?1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells

Bello-DeOcampo, Diana; Kleinman, Hynda K.; Deocampo, Nestor D.; Webber, Mukta M.

doi:10.1002/1097-0045(20010201)46:2<142::aid-pros1018>3.0.co;2-b

Cited by 73 publications

(27 citation statements)

References 27 publications

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“…5C). These results differed from other studies, where acinar formation of normal prostate epithelium was practically obliterated by the addition of either α6- or β1-blocking antibodies (18), but does agree with the fact that β1-integrin is more associated with the formation of focal adhesion complexes involved with motility than stable hemidesmosomal attachment sites used more for the anchoring of cells. To our knowledge, this is the first time that the effect of α6-, β1-integrin function-blocking antibodies has been tested against metastatic prostate cells rather than normal prostate epithelial in 3D, a more relevant assay for determining how changes in protein expression contribute to tumor progression.…”

Section: Resultscontrasting

confidence: 99%

“…In our study the interruption of α6- or β1-integrin expression reversed the morphological phenotype of the metastatic M12 subline back to organized, polarized acini in 3D as proposed, but never proven experimentally (5). Although β1-integrin inhibitory antibodies were shown to block acini formation in a previous study, cells were plated on top of LrECM and had to first move into the gel to subsequently form acini, addressing a different experimental question than here (18). Our results suggest that α6- or β1-integrin blocking antibodies could represent a relevant therapy to combat prostate tumor progression as has been suggested for metastatic breast cancer (41).…”

Section: Discussionmentioning

confidence: 94%

“…For example, RWPE-1, an immortalized, non-tumorigenic prostate epithelial cell line, was able to migrate into- and form branches terminating in- acini when plated on top of lrECM gels (2). However, NMU-transformed RWPE-1 cells formed solid cell masses (18). Cultures of RWPE-2, a Ki-ras transformed subline of RWPE-1, resulted in single to small clumps of cells with no evidence of acinus organization.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of vimentin or β1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Zhang

Fournier

Ware³

et al. 2009

Molecular Cancer Therapeutics

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Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to B-catenin, E-cadherin, or A 6 and B 1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of A 6 and B 1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and B 1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499 -508]

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Section: Resultscontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Inhibition of vimentin or β1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Zhang

Fournier

Ware³

et al. 2009

Molecular Cancer Therapeutics

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“…These results document that the addition of IFN to low Ca 2+ SFD culture medium allows intermediate cells to enhance their expression of AR protein but does not induce full differentiation of these cells toward the PSA + luminal-secretory phenotype. Notably, these findings are consistent with previous reports of RWPE-1 cells being able to undergo limited differentiation and acinar formation in three-dimensional Matrigel cultures in the presence of added androgen (37,38). Such ability of RWPE-1 cells to undergo acinar differentiation is further suggestive of the presence of prostate stem cells in these cultures.…”

Section: Resultssupporting

confidence: 92%

Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells

et al. 2006

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Stage-specific differentiation markers were used to evaluate the cellular composition and the origin of nonimmortalized (PrEC) and immortalized (PZ-HPV7, CA-HPV10, RWPE-1, and 957E/hTERT) human prostate cell lines. These studies documented that immortalized and nonimmortalized prostate epithelial cells established and maintained in low (i.e., <300 Mmol/L) Ca 2+ serum-free defined (SFD) medium were all derived from normal nonmalignant prostate tissues and contain CD133

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“…We do note one exception to this correlation, namely the most aggressive RWPE1-derived cell line, WPE1-NB26. The latter has received significant attention due to its highly invasive phenotype [30], [44]–[53]. Using total Src content and specific activity as measures of aggressiveness, we would have assigned a non-invasive phenotype to WPE1-NB26 (i.e.…”

Section: Discussionmentioning

confidence: 99%

Src Kinase Regulation in Progressively Invasive Cancer

Allbritton

Lawrence

2012

PLoS ONE

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Metastatic progression is a multistep process that involves tumor growth and survival, motility and invasion, and subsequent proliferation in an inappropriate environment. The Src protein tyrosine kinase has been implicated in many of the biochemical pathways that drive these behaviors. Although Src itself is only rarely mutated in human tumors, its aberrant activity has been noted in various cancers and suggested to serve as a barometer of metastatic potential. With these features in mind, we examined Src kinase regulation at the structural, enzymatic, and expression levels as a function of progressively invasive prostate cancer cell lines. Surprisingly, both total Src content and kinase activity decrease with increasing cell line aggressiveness, an observation that appears to be inconsistent with the well-documented role of Src in the signaling pathways that drive growth and invasion. However, we do observe a direct correlation between Src kinase specific activity (total Src kinase activity/total Src content) and metastatic aggressiveness, possibly suggesting that in highly aggressive cell lines, key signaling enzymes are globally recruited to drive the cancerous phenotype. In addition, although the expected enhanced phosphorylation of Src at Tyr-416 (activation site) is present in the most aggressive prostate cancer cell lines, unexpectedly high phosphorylation levels at the Tyr-527 inhibitory site are observed as well. The latter, rather than representative of inhibited enzyme, is more indicative of primed Src responsive to local phosphorylated binding partners.

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Laminin-1 and ?6?1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells

Cited by 73 publications

References 27 publications

Inhibition of vimentin or β1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Inhibition of vimentin or β1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells

Src Kinase Regulation in Progressively Invasive Cancer

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