Reference SummaryGruys ME, Cancer Res 2001 Aug 15;61(16):6255-63

Title

Induction of transplantable mouse renal cell cancers by streptozotocin: in vivo growth, metastases, and angiogenic phenotype.

Authors

Gruys ME; Back TC; Subleski J; Wiltrout TA; Lee JK; Schmidt L; Watanabe M; Stanyon R; Ward JM; Wigginton JM; Wiltrout RH

Journal

Cancer Res

Volume

61

Issue

16

Year

2001

Pages

6255-63

Abstract

Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal models of kidney cancer. We have used streptozotocin, an antibiotic and diabetogenic nitrosamine compound derived from Streptomyces achromogenes to induce new kidney tumors in BALB/c mice. Single or multiple doses of streptozotocin induced kidney tumors in up to 25% of mice by 50-90 weeks of age, with up to 18% characterized as renal cell carcinomas (RCCs). Several transplantable lines were obtained from the RCCs, and one of these lines was subsequently cloned. The initial tumor isolates and sublines were histologically reconfirmed to be RCCs, and all grew progressively but slowly (mean survival times, 57 to >100 days) in vivo after intrarenal implant. None of the primary isolates or sublines revealed mutations in either the VHL or Ras genes, although karyotype analysis and chromosome painting revealed the consistent presence of a submetacentric chromosome resulting from the fusion of chromosomes 16 and 19. Biological characterization of these tumors revealed several features analogous to the growth of human kidney cancers, including a propensity for the formation of lung metastases and high vascularity. This hypervascularity is evident by both gross and microscopic analysis and correlates with the expression of several proangiogenic genes. Overall, the features of orthotopic transplantability, slower in vivo growth (relative to the rapid growth rates of other transplantable mouse kidney tumors), propensity for lung metastases, and hypervascularity may make these tumors valuable models for the study of new therapeutic strategies based on antineovascular agents and antitumor cytokines.

Links

J:70901 – MGI References
11507080 – National Library of Medicine/PubMed

Strain Notes

Strain Note
BALB/cNcr These mice were originally obtained from the National Cancer Institute-Frederick Cancer Research and Development Center.
C57BL/6NCr These mice were originally obtained from the National Cancer Institute-Frederick Cancer Research and Development Center.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
BALB/cNcr Kidney adenoma
  • streptozotocin
Kidney

6.1

C57BL/6NCr Kidney adenoma
  • streptozotocin
Kidney

0.6

BALB/cNcr Kidney carcinoma
  • streptozotocin
Kidney

3.3 - 18

C57BL/6NCr Kidney carcinoma
  • streptozotocin
Kidney

0 - 0.6

BALB/cNcr Kidney tumor
  • streptozotocin
Kidney

24

C57BL/6NCr Kidney tumor
  • streptozotocin
Kidney

1.1

BALB/cNcr Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • streptozotocin
Leukocyte - Monocyte - Macrophage - Histiocyte

0.6

C57BL/6NCr Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • streptozotocin
Leukocyte - Monocyte - Macrophage - Histiocyte

0.6

BALB/cNcr Leukocyte lymphoma
  • streptozotocin
Lymph node

1.1

C57BL/6NCr Leukocyte lymphoma
  • streptozotocin
Lymph node

2.2

BALB/cNcr Liver adenoma
  • streptozotocin
Liver

1.1

BALB/cNcr Liver carcinoma
  • streptozotocin
Liver

0.6

BALB/cNcr Liver tumor
  • streptozotocin
Liver

1.7

BALB/cNcr Lung - Alveolus adenoma
  • streptozotocin
Lung - Alveolus

observed

BALB/cNcr Lung - Alveolus carcinoma
  • streptozotocin
Lung - Alveolus

observed

BALB/cNcr Lung - Bronchiole carcinoma
  • streptozotocin
Lung - Bronchiole

observed

BALB/cNcr Lung adenoma
  • streptozotocin
Lung

5.0

BALB/cNcr Lung carcinoma
  • streptozotocin
Lung

15

C57BL/6NCr Lung carcinoma
  • streptozotocin
Lung

0.6

BALB/cNcr Lung tumor
  • streptozotocin
Lung

20

BALB/cNcr (Unspecified organ) carcinoma
  • streptozotocin
(Unspecified organ)

0.6

BALB/cNcr (Unspecified organ) carcinoma
  • streptozotocin
Peritoneal cavity

0.6

BALB/cNcr (Unspecified organ) tumor
  • streptozotocin
(Unspecified organ)

31

C57BL/6NCr (Unspecified organ) tumor
  • streptozotocin
(Unspecified organ)

5.0

C57BL/6NCr (Unspecified organ) tumor - pleomorphic
  • streptozotocin
Lymph node

0.6