Antigenic heterogeneity and individuality in adenocarcinomas of the rectum and their secondaries

Enblad, Per; Glimelius, Bengt; Busch, Christer; Pontén, Jan; Påhlman, Lars

doi:10.1038/bjc.1987.102

Cited by 21 publications

(7 citation statements)

References 28 publications

(17 reference statements)

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“…Thus, antigenic heterogeneity was also an inherent characteristic of the studied cells. The total heterogeneity was as pronounced as has been reported in real human colon tumours [13] and in transplanted human colon tumours in immunodeficient rats [31. There was a tendency for binding of 38S1 antibodies in the central necrotic area of the HT-29 spheroids (Figs. 1, 2 and 4).…”

Section: Discussionmentioning

confidence: 55%

“…The reappearence of large amounts of CEA in carcinomas of the colon and its metastases, in carcinomas of the breast, bladder and lung [11,20] has led to the suggestion that radio-labelled antibodies against CEA should be used for localizing CEA-containing tumours [18,23,24] and maybe also for the targeting of cytotoxic radionuclides such as 131I [5,32,39] or 90y [21,33]. It has, with immuno-histochemical methods, been shown that the CEA expression in human colon carcinomas might be extremely heterogeneous [13]. Studies on transplanted human colon tumours in nude rats have also shown heterogeneous spatial distributions of monoclonal anti-CEA antibodies [3].…”

Section: Introductionmentioning

confidence: 99%

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Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids

Carlsson

Daniel-Szolgay

Frykholm

et al. 1989

Cancer Immunol Immunother

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The monoclonal antibodies 38S1, directed against the carcinoembryonic antigen (CEA), were tested for penetration and binding in human colon carcinoma HT-29 spheroids. Penetration was studied with a method which has not previously been used in immunological investigations. The method, which allows unbound substances to be visualized, is based on freeze drying, vapour fixation, dry sectioning and dry autoradiography. The antibodies penetrated easily and all parts of the HT-29 spheroids seemed to be reached within 15 min. The penetration was even faster than in control glioma U-118MG spheroids that did not express CEA. Binding of the 38S1 antibodies was demonstrated after processing with conventional histology and autoradiography. The binding in the HT-29 spheroids was, after a 1-h incubation period, extremely heterogeneous and occurred mainly in the peripheral parts. More cells were binding the antibodies after 8-h and 32-h incubations and these cells were arranged in peripheral clusters. No binding at all was seen in the CEA-negative glioma spheroids. The distribution of CEA antigens in monolayers and in frozen sections of spheroids of HT-29 cells was analysed with immunohistochemical staining using polyclonal CEA antibodies. The CEA antigens were heterogeneously distributed in both spheroids and monolayers and were as heterogenous as the binding of the monoclonal antibodies in the living spheroids. Thus, the heterogeneous binding in the living spheroids was not due to penetration barriers, but instead to the heterogeneity in the CEA antigen expression.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids

Carlsson

Daniel-Szolgay

Frykholm

et al. 1989

Cancer Immunol Immunother

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“…A similar technique with radiolabelled anti-CEA has been used for the in vivo detection of urinary bladder cancer (3). However, many tumour-associated antigens, including CEA, are often heterogeneously expressed within one and the same tumour, and also vary between tumours of the same morphological type and grades of differentiation (22,23). Therefore, a more universally expressed antigen was thought to be preferable for the immunoscintigraphic study of urothelial cancer.…”

Section: Antibodymentioning

confidence: 98%

Immunotargeting with Monoclonal Cytokeratin 8 Antibodies of Human Urothelial Cancer Transplanted to Nude Mice

Letocha

Nilsson

Silén³

et al. 1993

Acta Oncologica

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The possibility of using cytokeratin antibodies for the radioimmunolocalization of urinary bladder cancer was studied. A monoclonal murine IgG antibody was raised against cytokeratin 8 and labelled with iodine-125; normal murine IgG was used for control purposes. The urothelial cancer cell line RT4 was transplanted into immunodeficient nude mice. The anti-cytokeratin 8 antibody was administered intraperitoneally and its uptake in the tumour and other organs was analyzed with a computerized gamma camera. Optimal scintigraphic visualization occurred 11 days after antibody administration. The tumour/blood ratio of the specific antibody was 5.64 (+/- 5.01 SD) on day 11, compared with 0.73 (+/- 0.35 SD) in the control. Autoradiography demonstrated antibody uptake preferentially in viable sections of the tumour. The antibody uptake is presumed to be the result mainly of binding to the released cytokeratin in and around cells lysed during natural cellular death. The monoclonal murine anti-cytokeratin antibody is of potential interest in studies aimed at improving the clinical staging of urinary bladder cancer.

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“…Eine Unterscheidung zwischen einem nur auf die Mukosa begrenzten Tumorwachstum und einem die Mukosa überschreitenden scheint mittels CT kaum möglich[9].In dem hier vorgenommenen Vergleich waren die Tumormarker der CT-Untersuchung unterlegen: CEA mit einer Sensitivität von 0,63 und einer Genauigkeit von 0,72; CA19.9 entsprechend mit 0,25 und 0,59. Der Tumormarker CEA ist allgemein als Marker für das Rektumkarzinom akzeptiert[4,6,11,15]. Cascinu et al[4] betonten die Überlegenheit des CEA gegenüber dem CA19.9, ebenso von Kleist[11], die feststellte, dass die Kombination der beiden Tumormarker keine Vorteile brachte und dass CEA allein aussagekräftig war.…”

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“…Woche erschwerten. Enblad et al[6] untersuchten immunhistochemisch die Oberflächenantigenstruktur von Rektumkarzinomen. In 64 untersuchten Tumoren fanden sie CEA-positive Zellen mit einem Anteil von mehr als 90 %, während 37 % der Karzinome nur zu 10 % oder weniger CA19.9 exprimierten.…”

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Wertigkeit der Computertomographie und der Tumormarker zur Beurteilung von Lokalrezidiven beim operierten und nachbestrahlten Rektumkarzinom

Stückle¹,

Ibing²,

Adamietz³

2000

TumorDiagnostik & Therapie

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Antigenic heterogeneity and individuality in adenocarcinomas of the rectum and their secondaries

Cited by 21 publications

References 28 publications

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids

Immunotargeting with Monoclonal Cytokeratin 8 Antibodies of Human Urothelial Cancer Transplanted to Nude Mice

Wertigkeit der Computertomographie und der Tumormarker zur Beurteilung von Lokalrezidiven beim operierten und nachbestrahlten Rektumkarzinom

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