Peptide Hormones in Lung Cancer

259 Pages·1985·7.427 MB·English

by  J. M. Polak, S. R. Bloom (auth.), Professor Dr. Klaus Havemann, George Sorenson MD, Priv. Doz. Dr. Claus Gropp (eds.)

Recent Results 99
in Cancer Research
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Recent Results in Cancer Research
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Edited by H. Acker, J. Carlsson, R. Durand, R. M. Sutherland
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Volume 98: Peri operative Chemotherapy
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1985.48 figures, 45 tables. XII, 157. ISBN 3-540-15124-9
Peptide Hormones
in Lung Cancer
Edited by
K. Havemann, G. Sorenson, and C. Gropp
With 100 Figures and 63 Tables
Springer-Verlag Berlin Heidelberg GmbH
Professor Dr. Klaus Havemann
Klinikum der Philipps-Universitat Marburg
Zentrum fUr Innere Medizin
Medizinische Klinik und Poliklinik
Schwerpunkt Hamatologie, Onkologie, Immunologie
Baldingerstrasse, 3550 Marburg, FRG
George Sorenson, MD
Dartmouth Medical School
Department of Pathology
Hanover, NH 03756, USA
Priv. Doz. Dr. Claus Gropp
Klinik Bergisch-Land
Im Saalscheid 5, 5600 Wuppertal-Ronsdorf21, FRG
ISBN 978-3-540-15504-1 ISBN 978-3-642-82533-0 (eBook)
DOI 10.1007/978-3-642-82533-0
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Preface
The incidence of lung cancer has reached epidemic proportions
throughout the civilized world. One indication of the dimensions of
this problem is that in the United States lung cancer has become the
leading cause of cancer death in women as well as men. In 1912
there was a "nearly complete consensus of opinion that primary
malignant neoplasms of the lung (were one) of the rarest forms of
disease," according to Adler. By 1937, however, it had become clear
that the incidence of lung cancer was increasing significantly; this
increase has been progressive ever since.
It is now well known that some lung cancers give rise to a variety
of hormones which, at times, produce clinical manifestations. The
association of hormone production with a "nonendocrine" tumor
raises many questions, the answers to which may shed some light on
the etiology of this prevalent form of cancer. This fascinating prob
lem has stimulated a wide variety of studies in both the clinical and
the basic sciences. A number of the more recent studies in this field
were discussed at the International Symposium on Peptide Hor
mones and Lung Cancer held in Marburg, West Germany, on
June 18-20, 1984. This volume contains the papers that were pre
sented on this occasion.
Do the cell of origin for lung cancer produce hormones even be
fore the cancer develops? Or is this hormone production a pheno
typic alteration associated with malignant transformation? Cells
producing hormones such as calcitonin, bombesin, leu-enkephalin,
and neurotensin have been described in the bronchial mucosa. If
these cells are the cells of origin for lung cancer, then it follows that
these tumors can be considered comparable to other tumors derived
from endocrine celis already producing hormones. If, on the other
hand, a phenotypic alteration occurs, a different question arises:
Since hormone production occurs in all forms of lung tumors, in
cluding adenocarcinomas, why does it occur only rarely, if at all, in
adenocarcinomas arising in other tissues, such as the breast or colon?
Another issue discussed at the conference was the comparison of
hormone production in lung tumors and in normal cells. Is there a
VI Preface
difference between these two processes? If so, what does it consist
in? And if not, what can be learned about normal hormone produc
tion by studying hormone production in tumor cells? Much of the
current knowledge in this area has been gleaned from studies of
long-term cultures that have been established from lung tumor cells.
Several papers at the symposium dealt with this rewarding work.
Hopes were raised earlier that hormone production would prove
useful as a tumor marker for diagnostic purposes and also as a tool
for measuring the amount of tumor present and following the
course of tumor growth. These hopes have not been completely real
ized, though there have been some notable successes, which were
described at the symposium.
A major question in this area is: Can studies of hormones produc
tion lead to better methods of treatment? The answer to this ques
tion appears to be yes, insofar as the hormones produced by these
tumors may act as autocrine growth factors in many cases, so that
intervention in this process may lead to the inhibition of cell growth.
The introduction of molecular biological techniques has caused
an explosive increase in the range of laboratory techniques avail
able. These new approaches have shifted the emphasis of studies in
this area from the peptide hormone to the nucleic acid level, where
they focus either on mRNA or on the genome. This significant shift
in the scientific approach has prepared the way for exciting new dis
coveries in this field, many of which are presented in the papers con
tained in this volume.
K.Havemann
G. Sorenson
C. Gropp
Contents
Hormones and Neurotransmitters in Normal Lung . . . . . . 1
J. M. Polak and S. R. Bloom
Occurrence and Distribution of Regulatory Peptides in the
Respiratory Tract . . . . . . . . . . . . . . . . . . . . . . . . 1
K.L.Becker
Peptide Hormones and Their Possible Functions in the Normal
and Abnormal Lung . . . . . . . . . . . . . . . . . . . . . . . 17
J. Richardson
Neurotransmitters and Their Role in Pulmonary Physiology . . 29
Biochemistry of Peptide Hormones and Neurotransmitters
Produced by Lung Cancer . . . . . . . . . . . . . . . . . 34
H. P. J. Bennett
Peptide Hormone Biosynthesis - Recent Developments 34
J. G. Ratcliffe
ACTH and Related Peptides in Lung Cancer . . . . . . 46
L. H. Lazarus and 0. Hernandez
Physalaemin-Like Immunoreactivity from Human Lung Small
Cell Carcinoma: !socratic Reversed-Phase HPLC Analysis of
the Chemically Modified Peptide . . . . . . . . . . . . . . . . . 56
G.Milhaud
Calcitonin in Human Malignancies . 67
R. K. Craig, M. R. Edbrooke, J. H. Riley, J. H. Me Vey, and
D. Parker
Differential Expression of the Human Calcitonin- CGRP
Gene in Medullary Thyroid Carcinoma and Lung Carcinoma
Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
C. Gropp, W. Luster, and K. Havemann
Calcitonin in Lung Cancer . . . . . . . . . . . . . . . . . . . . 79
VIII Contents
H.-J. Schmelzer, R.-D. Hesch, and H. Mayer
Parathyroid Hormone and PTHmRNA in a Human Small Cell
Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
The Endocrine Lung Tumor Cell: In Vitro Studies . . . . . . . . 94
E. M. McDowell, K.-P. Keenan, and B. F. Trump
The Pathogenesis of Hormone-Producing Tumors of the Lung 94
K. Yamaguchi, K.Abe, !.Adachi, S.Kimura, M.Suzuki,
A. Shimada, T. Kodama, T. Kameya, and Y. Shimosato
Peptide Hormone Production in Primary Lung Tumors . . . . 107
W. Luster, C. Gropp, H. F. Kern, R. Wahl, H. D. Roher, and
K.Havemann
Peptide Hormone Production in Lung Cancer Cell Lines of
Different Histopathological Types . . . . . . . . . . . . . . . . 117
The Endocrine Lung Tumor Cell: Morphological Aspects . . . . 130
0. S. Pettengill, D. H. Wurster-Hill, C. C. Cate, and
G. D. Sorenson
Morphological Growth Characteristics and Hormone
Secretion of Small Cell Carcinoma of the Lung In Vitro . . . . 130
G. Sorenson, C. C. Cate, and 0. S. Pettengill
Regulation of Hormone Production in Small Cell Carcinoma
of the Lung ............................. 143
D. N. Carney, G. Bepler, and A. F. Gazdar
The Serum-Free Establishment and in Vitro Growth Properties
of Classic and Variant Small Cell Lung Cancer Cell Lines . . . 157
A. F. Gazdar, D. N. Carney, K. L. Becker, L. J. Deftos, V. Liang,
W. Go, P. J. Marangos, T. W. Moody, A. R. Wolften, and
M.H.Zweig
Expression of Peptide and Other Markers in Lung Cancer Cell
Lines ................................ 167
J. G. Reeve, M. Goedert, P. C. Emson, and N. M. Bleehen
Neurotensin in Human Small Cell Lung Carcinoma ...... 175
Clinical Implications of Peptide Hormone Production in Lung
Cancer ............................... 177
S.Krauss
Peptide Hormones as Tumor Markers in Lung Cancer Patients 177
M. Hansen and E. Bork
Peptide Hormones in Patients with Lung Cancer ........ 180
Contents IX
W. G. North, J. Ware, A. P. Chahinian, M. Perry, J. O'Donnell,
and L. H. Maurer
Clinical Evaluation of the Neurophysins as Tumor Markers in
Small Cell Lung Cancer . . . . . . . . . . . . . . . . . . . . . . 187
K. Havemann, R. Holle, and C. Gropp
Prospective Multicenter Study of Hormone Markers in Small
Cell Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . 194
General Aspects of Tumor Growth . . . . . . . . . . . . . . . . . 209
D. LeRoith and J. Roth
Syndromes Associated with Inappropriate Hormone Synthesis
by Tumors: An Evolutionary Interpretation . . . . . . . . . . . 209
U. R. Rapp, T.l. Bonner, K. Moe/ling, H. W. Jansen, K. Bister,
and J.Ihle
Genes and Gene Products Involved in Growth Regulation of
Tumor Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
C. A. Griffin and S. B. Bay/in
Oncogene Expression in Human Small Cell Lung Carcinoma . 237
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
List of Contributors*
Abe, K. 1071 Kameya, T. 107
Adachi, I. 107 Keenan, K.-P. 94
Bayl in, S. B. 237 Kern, H. F. 117
Becker, K. L. 17, 167 Kimura, S. 107
Bennett, H.P.J. 34 Kodama, T. 107
Bepler, G. 157 Krauss, S. 177
Bister, K. 221 Lazarus, L. H. 56
Bleehen, N.M. 175 LeRoith, D. 209
Bloom, S. R. 1 Liang, V. 167
Bonner, T. I. 221 Luster, W. 79, 117
Bork, E. 180 Marangos, P.J. 167
Carney, D. N. 157, 167 Maurer, L. H. 187
Cate, C. C. 130, 143 Mayer, H. 88
Chahinian, A. P. 187 McDowell, E. M. 94
Craig, R. K. 71 McVey, J.H. 71
Deftos, L.J. 167 Milhaud, G. 67
Edbrooke, M. R. 71 Moelling, K. 221
Emson, P.C. 175 Moody, T. W. 167
Gazdar, A. F. 157, 167 North, W.G. 187
Go, W. 167 O'Donnell, J. 187
Goedert, M. 175 Parker, D. 71
Griffin, C. A. 237 Perry, M. 187
Gropp, C. 79, 117, 194 Pettengill, 0. S. 130, 143
Hansen, M. 180 Polak, J. M. 1
Havemann, K. 79, 117, 194 Rapp, U.R. 221
Hernandez, 0. 56 Ratcliffe, J. G. 46
Hesch, R.-D. 88 Reeve, J.G. 175
Holle, R. 194 Richardson,]. 29
Ihle, J. 221 Riley, J. H. 71
Jansen, H. W. 221 Roher, H. D. 117
* The address of the principal author is given on the first page of each con
tribution
1 Page on which contribution begins