Skip to main content
Log in

Tumorigenic cell culture lines from a spontaneous VM/Dk murine astrocytoma (SMA)

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

One of the few spontaneous gliomas in inbred animals, the VM/Dk spontaneous murine astrocytoma (SMA), has seen limited use. Previously restricted to an in vivo system, the SMA was only transplantable intracerebrally (IC) using nonquantifiable suspensions of normal brain and tumor tissue. Prior atempts at establishing permanent tumorigenic SMA cell lines have not succeeded; tumorigenicity was lost during serial in vitro passage. We have established three different cell culture lines from a serially IC-transplanted SMA and two from tumors that arose from intraperitoneal (IP) injection of the IC-transplanted SMA. In contrast to previous cell cultures and transplantable lines of SMA, all five cell lines are not only tumorigenic IC but subcutaneously (SC) as well. Astrocytic features are present in three of five lines to varying degrees, evidenced by in vitro and in vivo morphology, response to dibutyryl cyclic AMP (db-cAMP), and the presence of neuroglial fibers: None of the lines express CNPase, S-100, or GFA proteins in significant amounts. P560, highly tumorigenic and possessing the most astrocytic features of the five lines, extends the use of the spontaneous astrocytoma system of the inbred VM/Dk mouse strain by allowing quantitative in vivo and in vitro experiments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albright L, Madigan JC, Gaston MR, Houchens DP (1975) Therapy in an intracranial murine glioma model, usingBacillus Calmette-Guerin, neuraminidase-treated tumor cells, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Cancer Res 35:658–665

    Google Scholar 

  • Ausman JI, Shapiro WR, Rall DR (1970) Studies on the chemotherapy of experimental brain tumors: development of an experimental model. Cancer Res 30:2394–2400

    Google Scholar 

  • Barker M, Hoshino T, Curcay O, Wilson CN, Nielsen SL, Downie R, Eliason J (1973) Development of a brain tumor animal model and its response to 1,3, bis (2-chloroethyl) 1-nitrosourea. Cancer Res 33:976–986

    Google Scholar 

  • Benda P, Someda K, Messer J, Sweet WH (1971) Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture. J Neurosurg 34:310–323

    Google Scholar 

  • Bigner DD, Swenberg JA (eds) (1977) Jänisch and Schreiber's Experimental Tumors of the central nervous system. Upjohn, Kalamazoo, MI

    Google Scholar 

  • Bigner DD, Self DJ, Frey J, Ishizaki R, Langlois A, Swenberg JA (1975) Refinement of the avian oncornavirus-induced primary rat brain tumor model and its potential for therapeutic screening. Recent Results Cancer Res 51:20–34

    Google Scholar 

  • Bigner DD, Bullard D, Schold C, Preissig SH, Wikstrand CJ (1979) Cellular heterogeneity and diversity as a basis for therapeutic resistance of human gliomas. Proceedings International Symposia Multidisciplinary Aspects of Brain Tumor Therapy. Elsevier, North Holland

    Google Scholar 

  • Bullard D, Preissig S, Pegram C, Bigner D (1978) In vitro response of cells derived from human gliomas (HGL) to dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP). J Neuropathol Exp Neurol 37:596

    Google Scholar 

  • Bullard DE, Bigner DD (1979) Animal models and virus induction of tumors. In: Thomas D, Graham D (eds) Brain tumors: Scientific basis, clinical investigation and current therapy. Butterworths, London, chapt 4

    Google Scholar 

  • Claisse PJ, Roscoe JP, Lantos PL (1979) Cellular heterogeneity in an ethylnitrosourea-induced glioma: malignancy, karyology, and other properties of tumor cell types. Br J Exp Pathol 60:209–224

    Google Scholar 

  • Copeland DD, Vogel FS, Bigner DD (1975) The induction of intracranial neoplasms by the inoculation of avian sarcoma virus in perinatal and adult rats. J Neuropathol Exp Neurol 34:340–358

    Google Scholar 

  • Dagle GE, Zwicker GM, Renne RA (1979) Morphology of spontaneous brain tumors in the rat. Vet Pathol 16:318–324

    Google Scholar 

  • Diters RW, Kircher CH, Nielsen SW (1978) Astrocytoma in a raccoon. J Am Vet Med Assoc 173:1152–1153

    Google Scholar 

  • Duch D, Mandel P, Koprowski H (1975) Demonstration of enzymes related to myelinogenesis in established human brain cell cultures. J. Neurol Sci 26:99–105

    Google Scholar 

  • Festenstein H (1976) The MLS system. Transplant Proc 8:339–342

    Google Scholar 

  • Fitzgerald JE, Schardein JL, Kurtz SM (1974) Spontaneous tumors of the nervous system in albino rats. J Natl Cancer Inst 1:265–273

    Google Scholar 

  • Fraser H (1971) Astrocytoma in an inbred mouse strain. J Pathol 103:266–270

    Google Scholar 

  • Fraser H (1975) Spontaneous astrocytomas in inbred mice: serial transmission studies with intact cells. In: Kornyey St, Tariska St, Gosztonyi G (eds) Proceedings of the VII International Congress of Neuropathology, vol 1, September 1–7, 1974, Budapest. Excerpta Medica, Amsterdam, pp 491–494

    Google Scholar 

  • Fraser H (1978) Viable cell transfer of spontaneous astrocytoma: differences in susceptibility between mouse strains. J Neuropathol Exp Neurol 37:614

    Google Scholar 

  • Gocke DJ, Howe C (1970) Rapid detection of Australia antigen by counter-immunoelectrophoresis. J Immunol 104:1031–1032

    Google Scholar 

  • Herman MM, Sipe JC, Rubinstein LJ, VandenBerg SR, Spence AM, Vraa-Jensen J (1975) An experimental mouse teratoma as a model for neuroepithelial neoplasia and differentiation. II. Electron microscopy. Am J Pathol 81:421–444

    Google Scholar 

  • Hewitt HB, Blake ER, Walder AS (1976) A critique of the evidence for active host defense against cancer, based on personal studies of 27 murine tumors of spontaneous origin. Br J Cancer 33:241–259

    Google Scholar 

  • Jacque CM, Kujas M, Poreau A, Raoul M, Collier P, Racadot J, Baumann N (1979) GFA and S-100 protein levels as an index for malignancy in human gliomas and neuromas. J Natl Cancer Inst 62:479–483

    Google Scholar 

  • Jungherr E; Wolf A (1939) Gliomas in animals. Am J Cancer 4:493–509

    Google Scholar 

  • Jurin, M, Suit HD (1972) In vivo and in vitro studies of the influence of the immune status of C3Hf/Bu mice on the effectiveness of local irradiation of a methylcholanthrene-induced fibrosarcoma. Cancer Res 32:2201–2211

    Google Scholar 

  • Kirschstein RL, Gerber P (1972) Ependymomas produced after intracerebral inoculation of SV40 into newborn hamsters. Nature 195:299–300

    Google Scholar 

  • Klein G, Klein E (1977) Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution. Proc Natl Assoc Sci USA 74:2121–2125

    Google Scholar 

  • Kurihara T, Nussbaum JL, Mandel P (1970) 2′,3′-cyclic nucleotide 3′-phosphohydrolase in brains of mutant mice with deficient myelination. J Neurochem 17:993–997

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Manoury R, Daumas-Duport C, Fontaine C, Vedrenne C (1979) Ultrastructural localization of glial fibrillary acidic protein (GFAP) in human glioma culture by immunoperoxidase method. Brain Res 170:392–398

    Google Scholar 

  • Prohaska JR, Clark DA, Wells WW (1973) Improved rapidity and precision in the determination of brain 2′,3′-cyclic nucleotide 3′-phosphohydrolase. Anal Biochem 56:275–282

    Google Scholar 

  • Rorke LB, Gilden DH, Wroblewska Z, Santoli D (1975) Human brain in tissue culture. IV. Morphological characteristics. J Comp Neurol 161:329–340

    Google Scholar 

  • Seligman AM, Shear MJ (1939) Studies in carcinogenesis. VIII. Experimental productions of brain tumors in mice with methylcholanthrene. Am J Cancer 37:364–395

    Google Scholar 

  • Swenberg JA, Koestner A, Wechsler W, Denlinger RH (1972) Quantitative aspects of transplacental tumor induction with ethylnitrosourea in rats. Cancer Res 32:2656–2660

    Google Scholar 

  • SundarRaj N, Schachner M, Pfeiffer SE (1975) Biochemically differentiated mouse glial cell lines carrying a nervous system specific cell surface antigen (NS-1). Proc Natl Acad Sci USA 72:1927–1931

    Google Scholar 

  • VandenBerg SR, Herman MM, Ludwin SK, Bignami A (1975) An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. I. Light microscopic and tissue and organ culture observations. Am J Pathol 79:147–168

    Google Scholar 

  • Wassenaar W, Tator CH, So WS (1973) The development of an intracerebral glioma model for brain tumor chemotherapy. J Neurosurg 39:293–301

    Google Scholar 

  • Wilson CB, Bates EA (1972) Transplantable brain tumors. In: Kirsch WM, Grossi-Paoletti E, Paoletti P (eds) The experimental biology of brain tumors. Thomas, Springfield, IL, pp 19–56

    Google Scholar 

  • Wilson CB (1978) Brain tumor models for experimental therapy. In: Laerum OD, Bigner DD, Rajewsky MF (eds) Biology of brain tumors, UICC technical report series, vol 30. International Union Against Cancer, Geneva, pp 185–199

    Google Scholar 

  • Wodinsky I, Kensler CJ, Rall DP (1969) The induction and transplantation of brain tumors in neonatal beagles. Proc Am Assoc Cancer Res 10:99

    Google Scholar 

  • Zimmerman HM, Arnold H (1941) Experimental brain tumors. I. Tumor produced with methylcholanthrene. Cancer Res 1:919–938

    Google Scholar 

  • Zuckerman JE, Herschman HR, Levine L (1970) Appearance of a brain-specific antigen (the S-100 protein) during fetal development. J Neurochem 17:247–251

    Google Scholar 

  • ZuRhein GM, Varakis J (1975) Morphology of brain tumors induced in Syrian hamsters after inoculation with JC virus, a new human papovarirus. In: Kornyer St, Tariska St, Gosztonyi G (eds) Proceedings of the VII International Congress of Neuropathology, vol 1, September 1–7, 1974, Budapest. Excerpta Medica, Amsterdam, p 479

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by NCI Grants CA 11898, CA 22790, and USPHS Grant 5T32-AG-00007

Rights and permissions

Reprints and permissions

About this article

Cite this article

Serano, R.D., Pegram, C.N. & Bigner, D.D. Tumorigenic cell culture lines from a spontaneous VM/Dk murine astrocytoma (SMA). Acta Neuropathol 51, 53–64 (1980). https://doi.org/10.1007/BF00688850

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688850

Key words

Navigation