Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice

Mostafa A Aboouf; Julia Armbruster; Franco Guscetti; Markus Thiersch; Andreas Boss; Axel Gödecke; Sandra Winning; Claudia Padberg; Joachim Fandrey; Glen Kristiansen; Anne Bicker; Thomas Hankeln; Max Gassmann; Thomas A Gorr

doi:10.1038/s41598-023-34614-w

Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice

Sci Rep. 2023 May 9;13(1):7530. doi: 10.1038/s41598-023-34614-w.

Authors

Mostafa A Aboouf^#^{1

2

3

4}, Julia Armbruster^#^{1

2

3}, Franco Guscetti⁵, Markus Thiersch^{1

4}, Andreas Boss⁶, Axel Gödecke⁷, Sandra Winning⁸, Claudia Padberg⁸, Joachim Fandrey⁸, Glen Kristiansen⁹, Anne Bicker^{10

11}, Thomas Hankeln¹⁰, Max Gassmann^{1

4}, Thomas A Gorr¹²

Affiliations

¹ Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland.
² Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057, Zurich, Switzerland.
³ Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
⁴ Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057, Zurich, Switzerland.
⁵ Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057, Zurich, Switzerland.
⁶ Department of Diagnostic and Interventional Radiology, University Hospital Zurich, 8091, Zurich, Switzerland.
⁷ Institute of Cardiovascular Pathology, Medical Faculty, Heinrich Heine University, 40225, Düsseldorf, Germany.
⁸ Institute for Physiology, University Duisburg-Essen, 47057, Essen, Germany.
⁹ Institute of Pathology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany.
¹⁰ Institute of Organismic and Molecular Evolution, Molecular and Genome Analysis, Johannes Gutenberg University, 55099, Mainz, Germany.
¹¹ University Medical Center Mainz, I. Medical Clinic, Langenbeckstr. 1, 55131, Mainz, Germany.
¹² Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland. tgorr@access.uzh.ch.

^# Contributed equally.

Abstract

Myoglobin (MB) is expressed in different cancer types and may act as a tumor suppressor in breast cancer. The mechanisms by which basal MB expression level impacts murine mammary tumorigenesis are unclear. We investigated how MB expression in breast cancer influences proliferation, metastasis, tumor hypoxia, and chemotherapy treatment in vivo. We crossed PyMT and WapCreTrp53^flox mammary cancer mouse models that differed in tumor grade/type and onset of mammary carcinoma with MB knockout mice. The loss of MB in WapCre;Trp53^flox mice did not affect tumor development and progression. On the other hand, loss of MB decreased tumor growth and increased tissue hypoxia as well as the number of lung metastases in PyMT mice. Furthermore, Doxorubicin therapy prevented the stronger metastatic propensity of MB-deficient tumors in PyMT mice. This suggests that, although MB expression predicts improved prognosis in breast cancer patients, MB-deficient tumors may still respond well to first-line therapies. We propose that determining the expression level of MB in malignant breast cancer biopsies will improve tumor stratification, outcome prediction, and personalized therapy in cancer patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biopsy
Carcinoma*
Disease Models, Animal
Hypoxia / genetics
Mice
Mice, Knockout
Myoglobin* / genetics

Substances

Myoglobin