Carcinoembryonic Antigen as a Selective Enhancer of Colorectal Cancer Metastasis

Hostetter, R.; Augustus, Lazel B.; Mankarious, R.; Chi, Kefung; Fan, Dominic; Toth, Christopher; Thomas, Peter; Jessup, J. Milburn

doi:10.1093/jnci/82.5.380

Cited by 182 publications

(103 citation statements)

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“…Increased CEA was found to be univariate adverse prognostic factor for survival in locally advanced or metastatic gastric cancer patients treated with first-line chemotherapy (Louvet et al, 2003). In our series, CEA 450 ng ml À1 was a negative prognostic factor and this may reflect the metastatic potential of malignant cells (Hostetter et al, 1990).…”

Section: Second-line Chemotherapy In Metastatic Gastric Cancer V Catasupporting

confidence: 47%

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

et al. 2008

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No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20 -40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16 -2.77; P ¼ 0.008), haemoglobin p11.5 g l À1 (HR, 1.48; 95% CI, 1.06 -2.05; P ¼ 0.019), CEA level 450 ng ml À1 (HR, 1.86; 95% CI, 1.21 -2.88; P ¼ 0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16 -2.53; P ¼ 0.006), and time-toprogression under first-line chemotherapy p6 months (HR, 1.97; 95% CI, 1.39 -2.80; Po0.0001). A prognostic index was constructed dividing patients into low-(no risk factor), intermediate-(one to two risk factors), or high-(three to five risk factors) risk groups, and median survival times for each group were 12.7 months, 7.1 months, and 3.3 months, respectively (Po0.001). In the absence of data deriving from randomised trials, this analysis suggests that some easily available clinical factors may help to select patients with advanced gastric cancer who could derive more benefit from second-line chemotherapy.

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Section: Second-line Chemotherapy In Metastatic Gastric Cancer V Catasupporting

confidence: 47%

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

et al. 2008

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“…Because the precise involvement of this tumour marker in the development of liver metastases cannot be analysed in humans, many studies have been conducted using animal models to try to demonstrate a connection between cause and effect. Most of the studies designed to address this question were based on the hypothesis that the adhesive properties of CEA might facilitate the development of liver metastases from colorectal cancer (Hostetter et al, 1990;Jessup et al, 1993a;Tibbetts et al, 1993;Thomas et al, 1995;Landuzzi et al, 1996). Recently, some authors suggested that CEA could enhance liver metastases via induction of cytokines in Kupffer cells (Gangopadhyay et al, 1996;Edmiston et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…To analyse the involvement of circulating CEA on the development of liver metastases from colorectal carcinoma in nude mice, Jessup et al (1993a) and Hostetter et al (1990) injected CEA i.v. 30 min before i.s.…”

Section: Discussionmentioning

confidence: 99%

“…In such cases, the CEA from the tumour is shed into the circulation and cleared by the liver where it binds first to Kupffer cells in which the terminal sialic acid residues are removed. Asialo-CEA is then transferred to hepatocytes where it is degraded (Hostetter et al, 1990;Gangopadhyay et al, 1996). An increase in circulating CEA levels thus corresponds to the saturation of the liver sites by the CEA shed from the tumour.…”

Section: Discussionmentioning

confidence: 99%

“…The question addressed in the present study was to determine whether these adhesive properties facilitate the development of liver metastases from colorectal cancer. Up to now, the involvement of CEA in the development of liver metastases from colorectal cancers has been addressed in two different ways: (i) comparison of the metastatic potential of different human colon carcinoma cell lines or CEA-transfected cells in association with CEA membrane expression (Tibbetts et al, 1993;Thomas et al, 1995;Landuzzi et al, 1996); (ii) analysis of the effect of circulating CEA on the development of liver metastases from different human colon carcinoma cells (Hostetter et al, 1990;Jessup et al, 1993a). This second approach is particularly interesting since one can imagine different strategies for modifying circulating CEA levels such as its capture with anti-CEA monoclonal antibodies (mAb).…”

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confidence: 99%

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Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Leconte¹,

Garambois²,

Ychou³

et al. 1999

Br J Cancer

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Summary Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEAcDNA truncated at its 3′ end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 µg CEA per 10 6 cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 × 10 6 CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml -1 for tumours ranging from 100 to 1000 mm 3 ), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

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Simplified Staging System for Predicting the Prognosis of Patients With Resectable Liver Metastasis

Minagawa

Yamamoto²,

Kosuge³

et al. 2007

Arch Surg

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Carcinoembryonic Antigen as a Selective Enhancer of Colorectal Cancer Metastasis

Cited by 182 publications

References 0 publications

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Simplified Staging System for Predicting the Prognosis of Patients With Resectable Liver Metastasis

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