Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

Marengo, Susan Ruth; Sikes, Robert A.; Anezinis, Ploutarchos; Chang, Shi‐Ming; Chung, Leland W.K.

doi:10.1002/(sici)1098-2744(199707)19:3<165::aid-mc4>3.0.co;2-d

Cited by 24 publications

(5 citation statements)

References 33 publications

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“…Moreover, HER‐2/ neu gene amplification and, to a lesser extent, p185 erb B‐2 protein expression have been correlated with increasing cancer grade1074, 1075 and androgen independence 1076. Experimental overexpression of p185 erb B‐2 in normal epithelial cells produces a phenotype with an increased rate of proliferation and enhanced capacity for metastasis 1077. A similar pattern of expression has been observed for the HER‐3 gene product p160 erbB‐3 in BPH, PIN, and cancer 1072.…”

Section: 0 Goalsmentioning

confidence: 63%

Human prostate cancer risk factors

Bostwick

Burke

Djakiew

et al. 2004

Cancer

516

359

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Section: 0 Goalsmentioning

confidence: 63%

Human prostate cancer risk factors

Bostwick

Burke

Djakiew

et al. 2004

Cancer

516

359

View full text Add to dashboard Cite

“…To gain further insight into the molecular events that lead to cancer metastasis and to establish useful experimental models of prostate can- cer metastasis, a number of approaches have been implemented. For example, genetic manipulation of prostate epithelial cells either through oncogene transfection [16][17][18] or transgenic mice using tissue-specific promoters [19][20][21] has resulted in low or no incidence of bone metastasis, with little evidence of osteoblastic reaction. Recognizing the importance of the tumorhost microenvironment interaction in dictating tumor behavior in vivo [4,22,23], we have derived human prostate cancer cell lines from tumor xenografts or their metastases by subculturing tumor cells from chimeric xenografts [3][4][5][6]8], and rat prostate cancer epithelial and stromal cell lines by altering the host microenvironment [9].…”

Section: Discussionmentioning

confidence: 99%

LNCaP progression model of human prostate cancer: Androgen‐independence and osseous metastasis

et al. 2000

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BACKGROUND.Clinically, the lethal phenotypes of human prostate cancer are characterized by their progression to androgen-independence and their propensity to form osseous metastases. We reported previously on the establishment of androgen-independent (AI) human prostate cancer cell lines derived from androgen-dependent (AD) LNCaP cells, with androgen independence defined as the capability of prostate cancer cells to grow in castrated hosts. One of the sublines, C4-2, was found to be AI, highly tumorigenic, and metastatic, having a proclivity for metastasis to the bone. METHODS. We established the AI and bone metastatic cell sublines B2, B3, B4, and B5 from the parental C4-2 subline, using a previously established coinoculating procedure. We determined the biologic behavior of the parental and derivative LNCaP sublines in vivo and in vitro, as well as their molecular and cytogenetic characteristics. RESULTS. Unlike other human prostate cancer models, the LNCaP progression model shares remarkable similarities with human prostate cancer. We observed a comparable pattern of metastasis from the primary to the lymph node and to the axial skeleton, with a predominant phenotype of osteoblastic reaction; 25-37.5% of the animals developed paraplegia. Cytogenetic and biochemical characterizations of LNCaP sublines also indicate close similarities between human prostate cancer and the LNCaP progression model. Additional chromosomal changes were detected in B2-B5 sublines derived from C4-2 bone metastases. These LNCaP sublines were found to grow faster under anchorage-dependent but not -independent conditions. The in vitro invasion and in vivo metastatic potential of these LNCaP sublines surprisingly correlated with anchorage-dependent and not -independent growth. The derivative LNCaP sublines when cultured in vitro produced a substantially higher (20-30-fold) amount of basal steady-state concentrations of PSA than that of the parental LNCaP cells. PSA production was high initially, but was markedly reduced when the derivative cell lines were inoculated and allowed to grow long-term in vivo for the establishment of tumors and metastasis, suggesting that unknown host factors derived either from the prostate or the bone can effectively downregulate PSA expression by prostate tumor epithelium. CONCLUSIONS. The LNCaP model of human prostate cancer progression will help improve our understanding of the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression.

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“…5,21,22 In the LAPC-4 prostate carcinoma model, much higher levels of HER-2 were found in androgen-independent sublines when compared with their androgen-dependent counterparts. 23 Furthermore, the same investigators showed that forced expression of HER-2/neu in androgen-dependent prostate carcinoma cells resulted in growth through ligand-independent activation of the androgen receptor pathway.…”

Section: Discussionmentioning

confidence: 99%

“…4 For example, when transfected into prostatic epithelial cell lines, HER-2 induces metastatic capacity in an orthotopic model. 5 It has also been postulated that the mechanism of the development of HRPC from its initial androgen-responsive form may be modulated through the androgen receptor with signaling through HER-2. 6 Overexpression of HER-2 occurs in approximately 20 -30% of patients with breast carcinoma and confers a poor prognosis.…”

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confidence: 99%

Trastuzumab plus docetaxel in HER‐2/neu‐positive prostate carcinoma

Lara

Chee

Longmate

et al. 2004

Cancer

101

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BACKGROUNDOverexpression of the HER‐2/neu oncoprotein has been reported to occur in ≤ 60% of patients with prostate carcinoma and to correlate with shortened survival. Trastuzumab is a humanized monoclonal antibody to the HER‐2 receptor and has activity against HER‐2–positive breast carcinoma, more so when combined with a taxane. The authors screened for HER‐2 overexpression in patients developing hormone‐refractory prostate carcinoma (HRPC) and conducted a Phase II trial of trastuzumab plus docetaxel in HER‐2–positive patients.METHODSParaffin‐embedded tumor specimens from potentially eligible patients were screened for HER‐2 expression by immunohistochemistry (IHC) and/or amplification by fluorescent in situ hybridization (FISH). Shed HER‐2 was also assessed by enzyme‐linked immunoradsorbent assay (ELISA). Patients with HER‐2–positive tumor specimens (IHC 2+ or 3+ or FISH ratio > 2) were initially randomized to receive either single‐agent trastuzumab or docetaxel. After two treatment cycles, nonresponding patients received the trastuzumab/docetaxel combination. Treatment was comprised of 30 mg/m2 of docetaxel weekly for 6 weeks followed by a 2‐week break and 4 mg/kg of trastuzumab intravenously during Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks.RESULTSOne hundred patients with HPRC were screened. IHC results were as follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed HER‐2 by ELISA (> 15 mg/mL). None overexpressed HER‐2 by IHC. FISH amplification was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score did not correlate with IHC status. Of the seven patients eligible for the Phase II study, only four agreed to participate. The trial was thus closed for nonfeasibility (the overall HER‐2 positivity rate was < 20%). No patient responded to trastuzumab alone. The median survival was not reached and the median progression‐free survival was 7 months.CONCLUSIONSHER‐2 overexpression by IHC in archival prostate carcinoma specimens was infrequent. There was no apparent correlation among IHC, ELISA, and FISH, although the sample size was limited. Conclusions regarding the predictive value of HER‐2 status on outcome after trastuzumab‐based therapy were not reached and were only drawn after larger‐scale screening efforts. The authors estimated that 1000 patients need to be screened to complete accrual to a 40‐patient efficacy trial. Cancer 2004. © 2004 American Cancer Society.

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Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

Cited by 24 publications

References 33 publications

Human prostate cancer risk factors

Human prostate cancer risk factors

LNCaP progression model of human prostate cancer: Androgen‐independence and osseous metastasis

Trastuzumab plus docetaxel in HER‐2/neu‐positive prostate carcinoma

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