Localization of bombesin-like peptides in tumors

J. M. Polak, Q. Hamid, D. R. Springall, F. Cuttitta, Eliot Spindel, M. A. Ghatei, S. R. Bloom

Research output: Contribution to journalArticle

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Abstract

The localization of bombesin gene products in neuroendocrine tumors was achieved by a number of techniques used in combination. These included immunocytochemistry, radioimmunoassay, and chromatographic procedures using a variety of region-specific antibodies recognizing separate portions of probombesin. In situ hybridization using cRNA probes was employed to analyse bombesin gene expression at a cellular level. A novel procedure using a divalent form of bombesin and gold-labeled monoclonal antibodies for the localization of bombesin binding sites at the ultrastructural level was employed in this study. Antibodies to neuron-specific enolase and electron microscopy were employed for the determination of neuroendocrine differentiation. Surgical samples of pulmonary (n=250) and nonpulmonary (n=28) small cell carcinomas, 49 carcinoids, and 62 atypical lung carcinoids were investigated and compared with 169 control tumors, including lymphomas, adenocarcinomas, squamous cell carcinomas, and non-small-cell undifferentiated tumors. Cell lines cultured from pulmonary small cell carcinoma and smear preparations of pleural effusions from patients with small cell carcinoma of the lung were also investigated. Strong immunostaining for neuron-specific enolase was noted in all neuroendocrine tumors investigated, and no immunoreactivity was noted in control cases. Electron-dense neurosecretory granules were abundant in carcinoid tumors, scattered in small cell carcinoids, and absent in control cases. Immunostaining for bombesin was particularly strong in benign carcinoids, whereas the more malignant neuroendocrine tumors (e.g., small cell carcinomas) stained best with antibodies to the carboxyl-terminal flanking portion of human probombesin (proGRP). These findings were further validated by radioimmunoassay and chromatography of tissue extracts. Specific binding sites for bombesin were demonstrated on the surface of small cell carcinoma cells maintained in culture. In situ hybridization demonstrated mRNA for preprobombesin in all small cell carcinomas investigated, including surgical samples, cytological preparations, and cell lines. Hybridization reactions varied in intensity, with some cells in autoradiograms almost masked by silver grains and others showing much lighter deposits.

Original languageEnglish (US)
Pages (from-to)322-335
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume547
StatePublished - 1989
Externally publishedYes

Fingerprint

Bombesin
Small Cell Carcinoma
Carcinoid Tumor
Tumors
Cells
Peptides
Neuroendocrine Tumors
Neoplasms
Phosphopyruvate Hydratase
Lung
Radioimmunoassay
In Situ Hybridization
Antibodies
Binding Sites
Cell Line
Complementary RNA
Tissue Extracts
Small Cell Lung Carcinoma
Pleural Effusion
Silver

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Polak, J. M., Hamid, Q., Springall, D. R., Cuttitta, F., Spindel, E., Ghatei, M. A., & Bloom, S. R. (1989). Localization of bombesin-like peptides in tumors. Annals of the New York Academy of Sciences, 547, 322-335.

Localization of bombesin-like peptides in tumors. / Polak, J. M.; Hamid, Q.; Springall, D. R.; Cuttitta, F.; Spindel, Eliot; Ghatei, M. A.; Bloom, S. R.

In: Annals of the New York Academy of Sciences, Vol. 547, 1989, p. 322-335.

Research output: Contribution to journalArticle

Polak, JM, Hamid, Q, Springall, DR, Cuttitta, F, Spindel, E, Ghatei, MA & Bloom, SR 1989, 'Localization of bombesin-like peptides in tumors', Annals of the New York Academy of Sciences, vol. 547, pp. 322-335.
Polak JM, Hamid Q, Springall DR, Cuttitta F, Spindel E, Ghatei MA et al. Localization of bombesin-like peptides in tumors. Annals of the New York Academy of Sciences. 1989;547:322-335.
Polak, J. M. ; Hamid, Q. ; Springall, D. R. ; Cuttitta, F. ; Spindel, Eliot ; Ghatei, M. A. ; Bloom, S. R. / Localization of bombesin-like peptides in tumors. In: Annals of the New York Academy of Sciences. 1989 ; Vol. 547. pp. 322-335.
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AU - Ghatei, M. A.

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