motilin and Lung-Neoplasms

The in vitro motility of B16-F1 melanoma cells is enhanced by incubation with a monoclonal antibody against gp78, previously characterized as a motility factor receptor. This antibody was used to study the relationship between motility stimulation in vitro and metastatic ability in vivo in the B16-F1 and K-1735 murine melanoma systems. While both high- and low-metastatic variants exhibited enhanced in vitro motility in response to the anti-gp78 monoclonal antibody, only the high-metastatic cells exhibited an increased metastatic ability. Surface immunofluorescence of low-metastatic cells was distributed more diffusely compared to a highly localized patching of gp78 on high-metastatic cells, suggesting that the directed endocytosis of gp78 to form a single leading edge is related to the metastatic ability of a cell, while fluorescence-activated cell sorter analysis revealed decreased gp78 surface expression in high-metastatic clones. Priming of cells by preventing internalization of gp78-antibody complexes by pertussis toxin resulted in a marked enhancement of pulmonary metastases by the treated cells which was directly correlated with decreased surface expression of gp78 following washout of pertussis toxin. These results suggest that cell motility induced by motility factor receptor occupancy may play a role in the process of metastasis and that the ligand-receptor complex internalization from the cell surface is involved in control of cell kinesis during metastasis.

Topics: Animals; Antigens, CD; Cell Line; Cell Movement; Flow Cytometry; Fluorescent Antibody Technique; Lung Neoplasms; Lysosomal Membrane Proteins; Melanoma, Experimental; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Motilin; Neoplasm Metastasis; Pertussis Toxin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Virulence Factors, Bordetella

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Small Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Motilin; Pancreatic Polypeptide; Prospective Studies; Retrospective Studies; Somatostatin; Vasoactive Intestinal Peptide