Kristiina Joensuu1, Päivi Heikkilä, Leif C Andersson. 1. Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Central Hospital, P.O. Box 21, Haartmaninkatu 3, FI-00290 Helsinki, Finland.
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.
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.
Authors: Kristen D Brantley; Anders Kjærsgaard; Deirdre Cronin-Fenton; Rami Yacoub; Anja S Nielsen; Kristina L Lauridsen; Stephen Hamilton-Dutoit; Timothy L Lash Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-03-28 Impact factor: 4.254
Authors: James M Haughian; Mauricio P Pinto; J Chuck Harrell; Brian S Bliesner; Kristiina M Joensuu; Wendy W Dye; Carol A Sartorius; Aik Choon Tan; Päivi Heikkilä; Charles M Perou; Kathryn B Horwitz Journal: Proc Natl Acad Sci U S A Date: 2011-10-03 Impact factor: 11.205