Gw-39: A New Human Tumor Serially Transplantable in the Golden Hamster

Goldenberg, David M.; Witte, Siegfried; Elster, K

doi:10.1097/00007890-196611000-00013

Cited by 93 publications

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“…Female athymic nude mice (6 to 8 weeks old) were purchased From Taconic (Germantown, NY). Therapy studies were done using our CEACAM5+/CEACAM6+ GW-39 intrapulmonary micrometastasis model, GW-39iv (40)(41)(42). The GW-39 human colonic carcinoma has been maintained as a serially transplanted signet-ring cell cancer line since 1966 (42).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)

2005

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CEACAM5 and CEACAM6 are overexpressed in many cancers and are associated with adhesion and invasion. The effects of three monoclonal antibodies targeting different epitopes on these antigens (NH 2 -terminal and A1B1 domains shared by CEACAM5 and CEACAM6 and the A3B3 domain restricted to CEACAM5) were evaluated in migration, invasion, and adhesion assays in vitro using a panel of human pancreatic, breast, and colonic cancer cell lines, and in the GW-39 human colonic micrometastasis model in vivo. MN-3 FabV and MN-15 FabV were both effective at inhibiting cell migration. MN-15 FabV treatment inhibited invasion, reducing cell penetration through an extracellular matrix (ECM). MN-3 FabValso decreased invasion but was less effective than MN-15 FabV in four of five cell lines. All three monoclonal antibody (mAb) Fabs decreased adhesion of tumor cells to endothelial cells by 49% to 58%. MN-15 FabV but not MN-3 or MN-14 Fabs induced a decrease in adhesion of three of six cell lines to the ECM protein, fibronectin, but adhesion to vitronectin, laminin, collagen-I, and collagen-IV was not affected. In vivo studies showed that treatment with MN-3 FabV or MN-15 FabV of mice implanted with GW-39 human colonic cancer cells increased their survival (P < 0.025 and P < 0.01, respectively). These studies show that antibody Fabs that target either CEACAM5 or CEACAM6 affect cell migration, cell invasion, and cell adhesion in vitro, and that MN-15 and MN-3 Fabs have antimetastatic effects in vivo, resulting in improved survival of mice with metastases. Thus, blocking the N and A1B1 domains of CEACAM5/CEACAM6 can impede the metastatic process.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)

2005

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“…In the case of GPI, our experiments have demonstrated a higher activity in GW-39 tumours as compared to either normal hamster tissues, normal human colon, or primary human colonic adenocarcinoma. The significantly increased level of GPI activity in GW-39 tumours, as compared to primary human colonic cancer, raises the question of whether our colonic cancer xenograft may be more reflective of metastatic than of primary colonic cancer, although this tumour was originally grafted directly from a specimen of sigmoid colon adenocarcinoma (Goldenberg et al, 1966). This view is supported by the earlier findings of Cooper et al (1975) and Munjal et al (1975and Munjal et al ( , 1976 for several other enzymes which, together with CEA, were found to be considerably elevated in the sera and tumour extracts of patients with colorectal cancers metastatic to the liver, and our own recent observations that metastatic colonic cancer has higher GPI activity than primary colonic cancer (Munjal, Zamcheck, and Goldenberg, in preparation).…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies of cancer patients have indeed shown that some of these enzymes can increase diagnostic accuracy in breast, lung and colorectal cancers when combined with the plasma CEA test (Steele et al, 1974;Cooper et al, 1975;Mun.jal et al, 1976). As a corollary to these initial clinical studies, we have undertaken an evaluation of the circulating levels of CEA and GPI in hamsters bearing a xenografted human colonic carcinoma, (Goldenberg, Witte and Elster, 1966), in order to study certain relationships of these two putative tumour markers in a human tumour model. Goldenberg et al (1966), and consists of injecting 0-1 ml of a 10 to 20% (w/v) tumour cell suspension into the growth site.…”

mentioning

confidence: 99%

“…As a corollary to these initial clinical studies, we have undertaken an evaluation of the circulating levels of CEA and GPI in hamsters bearing a xenografted human colonic carcinoma, (Goldenberg, Witte and Elster, 1966), in order to study certain relationships of these two putative tumour markers in a human tumour model. Goldenberg et al (1966), and consists of injecting 0-1 ml of a 10 to 20% (w/v) tumour cell suspension into the growth site. Expansively-growing, mucin-producing, signet-ring-cell carcinomas result, in almost all animals grafted.…”

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Carcinoembryonic antigen and glucose phosphate isomerase in a human colonic cancer model (GW-39)

Munjal¹,

Goldenberg²

1976

Br J Cancer

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Summary.-Levels of carcinoembryonic antigen (CEA) and glucose phosphate isomerase (GPI) have been compared in the circulating blood of hamsters bearing intra-muscular grafts of GW-39 human colonic tumour. CEA in the sera of GW-39 tumour-bearing hamsters ranged from 2 6 to 8-4 ng/ml (mean = 4-5 ± 1-7 ng/ml). GPI in the sera of normal hamsters ranged from 332 to 749 iu/l (mean = 602 ± 110 iu/l) while those with 14-week-old intra-muscular grafts of a hamster amelanotic melanoma, (A.Mel.3), or GW-39 human colonic carcinoma had a range of 664 to 1267 iu/l (mean = 1024 + 220 iu/l) and 1430 to 4719 iu/l (mean -2065 ± 601 iu/l) respectively.Thus, the ratio of enzyme activity in GW-39, A.Mel.3, and normal hamsters was 3 4:1-7:1, indicating a significant elevation (P < 0.01) in animals bearing a human colon carcinoma or a hamster melanoma, with particularly high values obtained in hamsters with GW-39.Sequential determinations of CEA and GPI in a group of hamsters transplanted intra-muscularly with GW-39 tumours revealed that both markers increased proportionately with duration of tumour growth, suggesting that both serum CEA and GPI may be used as measures of tumour growth. The concentration of GPI in GW-39 human colonic carcinoma xenografts was also significantly higher than that measured in normal human colon, primary human colonic cancer, or normal hamster tissues. These results support the view that GPI, in addition to CEA, is a quantitatively increased marker in this tumour model, and is liberated into the circulation in proportion to the increase in tumour mass.

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“…No host-conditioning was employed. Our method of hamster cheek pouch transplantation has also been described previously (Goldenberg, 1967;Goldenberg, Witte and Elster, 1966).…”

Section: Transplantation Studiesmentioning

confidence: 99%

Histogenetic Relationship Between Carcinoids and Mucin-secreting Carcinomas of Colon as Revealed by Heterotransplantation

Goldenberg¹,

Fisher²

1970

Br J Cancer

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Heterotransplantation of a human colonic neoplasm with classical morphologic characteristics of a carcinoid was sucessful in the cheek pouches of unconditioned, adult golden hamsters after a short sojourn in cell-impermeable chambers in rats. Although no mucin-secreting cells were detected in the donor carcinoid, the cheek pouch transplants exclusively exhibited mucinsecreting tumour cells of signet-ring type consistent with adenocarcinoma. This transplantable tumour, designated GW-77, has retained this appearance as well as expansive growth characteristics in xenogeneic hosts for a period of 4 years. These findings represent strong biological evidence consonant with views, based upon morphological findings, advocating a histogenetic relationship between colonic carcinoid and adenocarcinoma. It is believed that colonic adenocarcinoma has a selective advantage over carcinoid for serial propagation in an alien environment, indicating the less differentiated nature of its cellular components. Since the donor carcinoid cells failed to exhibit argentaffin reactions, these conclusions may be limited only to the nonreactive forms of carcinoid. Images Figs. 1-2 Figs. 3-4

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Gw-39: A New Human Tumor Serially Transplantable in the Golden Hamster

Cited by 93 publications

References 0 publications

Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)

Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)

Carcinoembryonic antigen and glucose phosphate isomerase in a human colonic cancer model (GW-39)

Histogenetic Relationship Between Carcinoids and Mucin-secreting Carcinomas of Colon as Revealed by Heterotransplantation

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