Abstract
In the United States, colon cancer is the most common form of internal cancer in both sexes. Prevention of the disease depends on early diagnosis of polyps or pre-cancerous lesions. The response of normal human colon fibroblasts (CRL1459) was used to identify individuals with clinical pre-cancer. Their plasma induced transformation associated morphology characterized by the retraction of cellular processes, cell rounding and eventual detachment from the vessel surface. Those plasma samples which induced a transformation associated morphology contained significantly increased levels of protease as shown by casein hydrolysis (Bio-Rad, CA). We are using hyperproteinasemia as a biomarker to identify individuals with polyps who have hereditary adenomatosis of the colon and rectum (ACR). We are currently evaluating cell cultures versus biochemical assays as a means for early detection of precancerous tumors in the general population. The findings of a tumor associated protease in clinical precancer, and its effect on cell cultures support our proposal that protease activity promotes tumor progression in ACR and may represent the gene defect in this hereditary disease.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Abbreviations
- ACR:
-
adenomatosis of the colon and rectum
- FPC:
-
familial polyposis coli
- GS:
-
Gardner syndrome
- VFPC:
-
variant familial polyposis coli
- TM:
-
transformed morphology
- PPA:
-
Plasma protease activity
- CEA:
-
carcinoembryonic antigen
- MNNG:
-
N′methyl N′ Nitroso N′ Nitrosoguanidine
- TPA:
-
12-O-tetradecanoyl phorbal—13 acetate
- PA:
-
plasminogen activator
- LETS:
-
Large External Transformation Sensitive protein
- C-AMP:
-
3′5′ cyclic adenosine monophosphate
- C-GMP:
-
3′5′ cyclic guanosine monophosphate.
References
American Cancer Society Facts and Figures, 1981.
H.J.R. Bussey, “Familial Polyposi Coli”, Johns Hopkins University Press, Baltimore, MD (1975).
C.R. Sachatello and W.O. Griffen, Familial polyposis coli, Am. J. Surg. 128:198, 1975.
V.A. McKusick, Genetics and colon cancer: A review, Digest Dis. 19(10):954, 1974.
T. Alm and B. Wahren, Carcinoembryonic antigen in hereditary adenomatosis of the colon and rectum. Scand. J. Gastroenterol. 19(8):875, 1975.
A.V. Jubert, T.M. Talbott and T.M. Maycroft, Characteristics of adenocarcinomas of the colorectum with low levels of preoperative plasma carcinoembryonic antigen (CEA), Cancer 42:635, 1978.
J.K. Isley, Jr. and R.B. Akin, A community-based colon and rectal cancer screening program. J. Florida M.A. July:501, 1981.
J.S. Rhim, R.J. Huebner, P. Arnstein and L. Kopelovich, Chemical transformation of cultured human skin fibroboasts derived from individuals with hereditary adenomatosis of the colon and rectum, Int. J. Cancer 16(5):565, 1980.
L. Kopelovich, N.E. Bias and L. Helson, Tumour promotors alone induces neoplastic transformation of fibroblasts from human genetically predisposed to cancer, Nature 282:619, 1979.
R. Pollack, et al., Production of plasminogen activator and colonial growth in semisolid medium are in vitro correlates of tumorigeneicity in the immune-deficient nude mouse. In: “Proteases and Control, Vol. 2, ” (Cold Springs Harbor Conference on Cell Proliferation), (E. Reich, D.B. Rifkin and E. Shaw, eds.) Cold Springs Harbor Laboratory, NY (1975).
L. Kopelovich, Hereditary adenomatosis of the colon and rectum. A model of tumor progression. In: “Cancer Invasion and Metastasis: Biological Mechanisms and Therapy,” (B.S. Day et al., eds.), Raven Press, NY., pp. 383–395 (1977).
S. Jaken and P.H. Black, Regulation of plasminogen activator in 3T3 cells: Effect of phorbol myristate acetate on subcellular distribution and molecular weight. J. Cell Biol. 90:727, 1981.
A.R. Kennedy and J.B. Little, Effects of protease inhibitors on radiation transformation in vitro. Cancer Res. 41(6):2103, 1981.
B.S. Danes and E.J. Gardner, The Gardner Syndrome: A cell culture study on kindred 109. J. Med. Genet. 15:346, 1978.
H.C. Lyko and J.X. Hartmann, Detection of plasma protease in heritable adenomatosis coli. Abstr. In: “Cancer Research Proceedings,” Waverly Press, Inc., Baltimore, MD 21:81, 1980.
H.C. Lyko and J.X. Hartmann, Plasma protease and inhibitor activity identifies patients with a precancerous condition. Dancer Detection and Prevention 3(1):326, 1980.
H.C. Lyko and J.X. Hartman, Familial polyposis coli plasma causes a transformation associated morphology of cells in vitro: Hyperproteinasemia and colorectal polyps, Cancer Detection and Prevention 4:401–405, 1981.
A. Vaheri, et al., Fibronectin and proteases in tumor invasion. European Organization for Research on Treatment of Cancer (EORTC) Monograph Series, In: “Proteinases and Tumor Invasion,” (P. Straeuli, A.J. Barrett and A. Baici, eds.) Raven Press, NY, pp. 49–58 (1980).
J.B. Boyd, et al., Production and secretion of proteolytic enzymes by normal and neoplastic cells. J. Surg. Oncol. 11(3):275, 1979.
P. Whur, J.J. Silcox, J.A. Boston and D.C. Williams, Plasminogen activation transforms the morphology of quiescent 3T3 cell monolayers and initiates growth, Br. J. Cancer 39(6):718, 1979.
S. Jaken and P.H. Black, Differences in intracellular distribution of plasminogen activator in growing, confluent, and transformed 3T3 cells. Proc. Natl. Acad. Sci. 76(1):246, 1979.
E. Wilmes, O.L. Schonberger and K. Hochstrasser, Studies for proteolysis in malignant tumours. Laryngol. Rhinol Otol. 58(11):861, 1979.
L. Kopelvich, et al., Organization of actin containing cables in cultured skin fibroblasts from individuals at high risk of colon cancer. Int. J. Cancer 26(3):301, 1980.
D.B. Rifkin, R.M. Crowe and R. Pollack, Tumor promotors induce changes in the chick embryo fibroblast cytoskeleton, Cell 18:361, 1979.
R. Pollack and D. Rifkin, Actin-containing cables within anchorage-dependent rat embryo cells are dissociated by plasmin and trypsin, Cell 6:495, 1975.
C. Kryceve-Martinerie, et al., Transformation-enhancing factor(s) released from chicken Rous sarcoma cells: Effect on some transformation parameters. Virol. 112(2):436, 1981.
G. De Petro, S. Bartali, T. Vartio and A. Vaheri, Transforming-enhancing activity of gelatin-binding fragments of fibronectin. Proc. Natl. Acad. Sci. 78(8):4965, 1981.
M.M. Burger, et al., Growth control and cyclic alterations of cyclic AMP in the cell cycle. Nature New Biol. 239:161, 1972.
F.R. DeRubertis, R. Chayoth and J.B. Field, The content and metabolism of cyclic adenosine 3′5′ monophosphate and cyclic guanosine 3′5′ monophosphate in adenocarcinoma of the human colon, J. Clin. Invest. 57:641, 1976.
M. Lipkin, Cell kinetics: Summary of recent findings in studies of gastro intestinal disease in man. J. Envir. Pathol. Toxicol. 2(1):9, 1978.
F.R. DeRubertis and P.A. Craven, Early alterations in rat colonic mucosal cyclic nucleotides metabolism and protein kinase activity induced by 1, 2,-Dimethylhydrazine, Cancer Res. 40:4589, 1980.
H.C. Lyko and J.X. Hartmann, Ascorbate, cyclic nucleotides, citrus and a model for preventing large bowel cancer. J. Theor. Biol. 83:675, 1980.
M.L. Pall, Gene-amplification model of carcinogenesis. Proc. Natl. Acad. Sci. 78:2465, 1981.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Plenum Press, New York
About this chapter
Cite this chapter
Lyko, H.C., Hartmann, J.X. (1984). Use of Cell Culture to Identify Human Precancer. In: Acton, R.T., Daniel Lynn, J. (eds) Eukaryotic Cell Cultures. Advances in Experimental Medicine and Biology, vol 172. Springer, New York, NY. https://doi.org/10.1007/978-1-4615-9376-8_27
Download citation
DOI: https://doi.org/10.1007/978-1-4615-9376-8_27
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4615-9378-2
Online ISBN: 978-1-4615-9376-8
eBook Packages: Springer Book Archive