Cadherin intercellular adhesion molecule in hepatocellular carcinomas: loss of E-cadherin expression in an undifferentiated carcinoma

Shimoyama, Yutaka; Hirohashi, Setsuo

doi:10.1016/0304-3835(91)90206-w

Cited by 179 publications

(95 citation statements)

References 13 publications

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“…Recent immunohistochemical findings of decreased Ecadherin in progressive tumours suggest that some change in the expression level of cell-surface E-cadherin apparently occurs in malignant tissues (Shimoyama & Hirohashi, 1991b;Rasbridge et al, 1993). This is the first investigation in which soluble cadherin has been found to be present in human biological fluids.…”

Section: Subjectsmentioning

confidence: 78%

“…Although the cadherin-catenin association is lost in some tumour cell lines or disturbed by oncogenic transformation (Shimoyama et al, 1992;Hamaguchi et al, 1993), there are no data available with regard to the prevailing mechanisms responsible for decreased E-cadherin staining in human tumour tissues (Shimoyama & Hirohashi, 1991b;Rasbridge et al, 1993). One of the answers to this could be supplied by the previous observation that a metastatic phenotype is induced by the genetic deletion of E-cadherin as an invasion suppressor (Chen & Obrink, 1991;Vleminckx et al, 1991).…”

Section: Subjectsmentioning

confidence: 99%

“…Many immunohistochemical studies searching for tissue distribution of cadherins have demonstrated that unstable or reduced expression of E-cadherin seems to be a common event in cancer progression, e.g. in lung carcinoma (Shimoyama et al, 1989), gastric tumours (Shimoyama & Hirohashi, 1991a), hepatocellular carcinoma (Shimoyama & Hirohashi, 1991b), breast carcinoma (Rasbridge et al, 1993) and prostatic tumours (Bussemakers et al, 1992;Umbas et al, 1992).…”

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confidence: 99%

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Soluble E-cadherin fragments increased in circulation of cancer patients

Katayama

Hirai²,

Kamihagi³

et al. 1994

Br J Cancer

168

131

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Summary Monoclonal antibodies were raised against human placental soluble E-cadherins and used in an immunoenzymometric assay to detect soluble E-cadherins in biological fluids. The E-cadherin assay was accurate enough to quantitate the concentration of soluble E-cadherin in the cell culture supernatants. Immunoreactive E-cadherins, identified as existing in the soluble form in normal serum, were shown to have apparent lower molecular mass (approximately 80 kDa) than intact molecules of E-cadherin. We found that the immunoreactive E-cadherin levels in the serum of the studied cancer patients were significantly elevated (mean ± s.d. 3.80 ± 2.36 tig ml', P<0.0001) when compared with the normal levels (1.99 ± 0.50 1tg ml-'). We also found that serum E-cadherin levels in the 22 patients with gastric cancer (3.51 ± 1.78 tLg ml-, P <0.02) or the 11 patients with hepatocellular cancer (5.55 ± 3.11 Lg ml-', P<0.001) were significantly higher than those in the 26 diabetic patients (2.33 ± 1.58 iLg ml-'). Of the 54 cancer patients, 53.7% exhibited an elevated amount of soluble E-cadherin in serum. Thus, it is evident that soluble E-cadherin in circulation can be used as a prospective tumour marker that accurately reflects the progressive regeneration of E-cadherin at tumour sites, potentially induced by tumour-associated proteolytic degradation.

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Section: Subjectsmentioning

confidence: 78%

Section: Subjectsmentioning

confidence: 99%

mentioning

confidence: 99%

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Soluble E-cadherin fragments increased in circulation of cancer patients

Katayama

Hirai²,

Kamihagi³

et al. 1994

Br J Cancer

168

131

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“…Loss of Ecadherin expression has been linked to the gain of invasive potential (Frixen et al, 1991;Vleminckx et al, 1991;Berx et al, 1995) and has recently been identified as the cause of hereditary gastric cancer (Guilford et al, 1998). LOHs at 16q have on one hand been observed in 40-70% of the cases in HCC studies (Nishida et al, 1992;Yeh et al, 1996) but have conversely been correlated with advanced stages (Nishida et al, 1992) and dedifferentiated morphology of HCC (Shimoyama and Hirohashi, 1991). Functional inactivation of E-cadherin in carcinomas may additionally arise epigenetically through hypermethylation (Graff et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

Niketeghad

Decker²,

Caselmann

et al. 2001

Br J Cancer

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Summary Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood. In order to search for common macroimbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (CGH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the cadherin gene cluster, some of them previously identified as potential target genes in HCC development. Several potential growth-or transformation-promoting genes located in chromosomal subregions showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gene relevant for HCC development.

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“…E-cadherin is also an important adhesion molecule in inhibiting tumour metastasis by connecting homophilic cells (Frixen et al, 1991). Its downregulation is implicated in metastasis of some malignant tumours (Shimoyama and Hirohashi, 1991;Miyasaka, 1995). uPA is a serine proteinase responsible for the degradation of ECM/BM and activation of hepatocyte growth factor (HGF) (Daikuhara et al, 1992;Ellis et al, 1992;Blasi, 1993).…”

Section: Extra Chromosomes Abnormal Chromosomes (Markers)mentioning

confidence: 99%

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis

et al. 1999

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Human hepatocellular carcinoma (HCC) is one of the most common types of tumour, especially in Asia and Africa (Anderson et al, 1992;Okuda, 1992;Parkin et al, 1993). HCC is characterized by extensive carcinoma cell infiltration and metastasis. Although advances have been made in liver cancer therapies, most cancer deaths still result from metastatic disease, so metastasis has been the greatest obstacle to successful tumour treatment. The poor understanding of the molecular mechanisms responsible for the disseminated metastasis, which would be partly due to the lack of ideal samples and models for study, has hindered the development of effective antimetastatic therapies. Although several reports of the establishment of HCC cell lines were available (Chen, 1963;Alexander et al, 1976;Dong et al, 1980), none have demonstrated prominent metastatic potential. The human cell line with a metastatic potential from primary tumour or metastatic lesions would permit metastatic mechanisms to be studied further. However, the cancer cells from the surgical samples or metastatic lesions can only be maintained in primary culture for a short time before cellular senescence occurs. The aim of this study was to establish a human HCC cell line with a metastatic potential. We successfully established a new HCC cell line with a highly metastatic potential derived from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) (Sun et al, 1996) by improving the conventional method of establishing a cell line -alternating cell culture in vivo and growth in nude mice. In this paper the processes of establishing a new human HCC cell line MHCC97 and some characteristics, including observation of some factors associated with metastasis, are reported. MATERIALS AND METHODS Specimens and in vitro cultureSeventy-eight primary cultures were taken from subcutaneous or intrahepatic xenografts of LCI-D20 nude mouse models. The model was developed by orthotopic inoculation of an intact tumour tissue of an intrahepatic disseminated lesion from a 39-year-old Chinese male patient with HCC (Zhong-Shan Hospital, Shanghai Medical University). Abnormal alpha-fetoprotein (AFP) and HBsAg were found in serum from this patient. The LCI-D20 model represents 100% metastases to the lungs, lymph nodes and intrahepatic spreading (Sun, 1996). These xenografts were removed and used for primary culture in vitro by different culture methods (tissue fragments or single-cell Summary A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited ty...

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Cadherin intercellular adhesion molecule in hepatocellular carcinomas: loss of E-cadherin expression in an undifferentiated carcinoma

Cited by 179 publications

References 13 publications

Soluble E-cadherin fragments increased in circulation of cancer patients

Soluble E-cadherin fragments increased in circulation of cancer patients

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis

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