Microenvironment-associated lymph node metastasis of human cervical carcinoma xenografts

Acta Oncol. 2012 Apr;51(4):465-72. doi: 10.3109/0284186X.2011.636751. Epub 2012 Jan 31.

Abstract

Background: The prognosis is particularly poor for patients with advanced squamous cell carcinoma of the uterine cervix when the primary tumor has developed severe physiological abnormalities. The impact of the physiological microenvironment of the primary tumor on lymph node metastasis was investigated in this preclinical study.

Material and methods: Xenografted tumors of two human cervical carcinoma lines (CK-160 and TS-415) transplanted into BALB/c nu/nu mice were included in the study. The fraction of radiobiologically hypoxic cells (HF(Rad)), interstitial fluid pressure (IFP), and extracellular pH (pH(e)) were measured in 22 CK-160 tumors and 16 TS-415 tumors and related to the metastatic status of the host mice.

Results: In CK-160, HF(Rad) was significantly higher in the metastatic than in the nonmetastatic tumors, whereas the metastatic and nonmetastatic tumors did not differ significantly in IFP or pH(e). In TS-415, IFP was significantly higher in the tumors that metastasized than in those that did not metastasize, whereas the tumors of the metastasis-positive and metastasis-negative mice did not differ significantly in HF(Rad) or pH(e).

Conclusion: Lymph node metastasis is associated with abnormalities in the physiological microenvironment of the primary tumor in cervical carcinoma xenografts, and tumor line-specific mechanisms are probably involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology*
  • Cell Hypoxia*
  • Extracellular Fluid*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Lymphatic Metastasis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pelvic Neoplasms / secondary*
  • Prognosis
  • Tumor Microenvironment*
  • Uterine Cervical Neoplasms / pathology*