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Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic.

Publication ,  Journal Article
Shi, Q; Abbruzzese, JL; Huang, S; Fidler, IJ; Xiong, Q; Xie, K
Published in: Clin Cancer Res
November 1999

The role and regulation of interleukin 8 (IL-8) in the growth and metastasis of SG, FG, and L3.3 variants derived from COLO 357 human pancreatic cancer cells were determined. After orthotopic implantation in the pancreas of nude mice, SG cells produced the smallest tumors, whereas L3.3 cells produced the largest tumors. SG cells produced no liver metastasis, whereas FG cells produced numerous liver metastases, and L3.3 cells produced more and larger liver metastases. In vitro analysis of IL-8 expression indicated that SG cells expressed the lowest level of IL-8 gene expression as determined by both Northern blot analysis and ELISA, whereas L3.3 cells expressed the highest level of IL-8. Immunohistochemical analysis of tumor lesions indicated that IL-8 overexpression was predominant in the regions surrounding necrotic areas, where cells were exposed to low oxygen tension (hypoxia) and acidic pH. In vitro treatment of FG tumor cells with hypoxia or acidosis led to an increased expression of IL-8. To directly determine the role of IL-8 in the growth and metastasis of pancreatic cancer, FG cells were transfected with IL-8 sense or antisense oligonucleotide expression vectors. The neo-resistance gene-transfected FG cells were used as controls. Decreased IL-8 expression after transfection with IL-8 antisense oligonucleotide expression vector retarded the growth of FG cells in mice after intrapancreatic implantation, which correlated with decreased tumor angiogenesis. Our data demonstrated that hypoxia and acidosis contribute to the overexpression of IL-8, which in turn plays an important role in tumor angiogenesis and contributes significantly to the aggressive biology of human pancreatic cancer.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 1999

Volume

5

Issue

11

Start / End Page

3711 / 3721

Location

United States

Related Subject Headings

  • Transfection
  • Recombinant Proteins
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Oligodeoxyribonucleotides, Antisense
  • Oligodeoxyribonucleotides
  • Neovascularization, Pathologic
  • Neoplasm Metastasis
  • Mice, Nude
  • Mice
 

Citation

APA
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Shi, Q., Abbruzzese, J. L., Huang, S., Fidler, I. J., Xiong, Q., & Xie, K. (1999). Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res, 5(11), 3711–3721.
Shi, Q., J. L. Abbruzzese, S. Huang, I. J. Fidler, Q. Xiong, and K. Xie. “Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic.Clin Cancer Res 5, no. 11 (November 1999): 3711–21.
Shi Q, Abbruzzese JL, Huang S, Fidler IJ, Xiong Q, Xie K. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res. 1999 Nov;5(11):3711–21.
Shi Q, Abbruzzese JL, Huang S, Fidler IJ, Xiong Q, Xie K. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res. 1999 Nov;5(11):3711–3721.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 1999

Volume

5

Issue

11

Start / End Page

3711 / 3721

Location

United States

Related Subject Headings

  • Transfection
  • Recombinant Proteins
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Oligodeoxyribonucleotides, Antisense
  • Oligodeoxyribonucleotides
  • Neovascularization, Pathologic
  • Neoplasm Metastasis
  • Mice, Nude
  • Mice