Tumor dormancy: elevated expression of stanniocalcins in late relapsing breast cancer

Cancer Lett. 2008 Jun 28;265(1):76-83. doi: 10.1016/j.canlet.2008.02.022. Epub 2008 Mar 19.

Abstract

Background: Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. The stanniocalcins (stanniocalcin-1, STC-1 and stanniocalcin-2, STC-2) are 56kDa homodimeric proteins. They act as pro-survival factors and contribute to the endurance of terminally differentiated cells such as neurons and adipocytes. We investigated whether elevated expression of stanniocalcins also plays a part in the tumor dormancy of breast cancer.

Methods: The expression of STC-1, STC-2 and estrogen receptor (ER) was studied by immunohistochemistry in 72 primary breast cancers and in their metastatic relapses detected before two years, or after 5 or 10 years from primary surgery.

Results: When compared to primary tumors with early relapse and their metastases, the expression of STC-1 and STC-2 was significantly higher in relapses occurring after five year (STC-1 p=0.0012, STC-2 p=0.004) and even higher in very late relapses occurring 10 years after surgery (STC-1 p=0.0017, STC-2 p=0.0001). Moreover, primary tumors with a propensity of very late relapse displayed a higher initial expression of STC-2 (p=0.0001). A significantly increased frequency of ER expression was found in the very late relapses.

Conclusion: These findings suggest that elevated expression of STC-1 or STC-2 act as survival factors also for breast cancer cells and thereby contribute to tumor dormancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Glycoproteins / biosynthesis*
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Receptors, Estrogen / biosynthesis
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Estrogen
  • STC2 protein, human
  • teleocalcin