Both precursor forms of
gastrin and mature amidated
gastrin peptides can enhance proliferation of colorectal tumours and may regulate growth in an autocrine manner. The purpose of this study was to evaluate the effect of neutralization of precursor and amidated
gastrin on primary and secondary in vivo growth of a human colorectal tumour. The human colorectal cell line, AP5LV, when injected into the muscle layer of the abdominal wall of severe combined immunodeficient (SCID) mice, grows as a well-vascularized primary tumour and
metastasis to the lung. AP5LV expressed the precursor
gastrin forms;
progastrin and
glycine-extended
gastrin and
gastrin/CCKB receptors, as assessed by immunocytochemistry.
Gastrimmune is a
gastrin immunogen in which the amino terminus of the
gastrin-17 molecule is linked to
diphtheria toxoid and induces
antibodies which neutralise the amidated and
glycine-extended forms of
gastrin-17. Rabbit antiserum, raised against
Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control animals were treated with antiserum raised against
diphtheria toxoid only.
Antibodies raised against
Gastrimmune significantly limited the growth of primary AP5LV tumours, as assessed by median cross-sectional area (controls = 244 mm2; antibody-treated = 179 mm2; P = 0.033). In addition
Gastrimmune-induced antiserum limited the growth of lung
metastasis as assessed by nodule number (controls = 3.5; antibody-treated = 1.0; P = 0.0001) and nodule cross-sectional as assessed by image analysis (controls = 11.9 mm2; antibody-treated = 3.75 mm2; P = 0.0064). In conclusion in vivo neutralization of
gastrin forms, which may potentially be fueling growth by an autocrine pathway, inhibited both primary growth and, to a greater degree, lung
metastasis of a human colorectal tumour cell line. Immunization against tumour-associated
gastrin forms may provide an effective
therapy for advanced
colorectal cancer.