Macrophages mediate a switch between canonical and non-canonical Wnt pathways in canine mammary tumors
Authors: Mikołaj Perszko
Joanna Mucha
Eva Hellmen
Alicja Majewska
Agata Homa
Kinga Majchrzak
Tomasz Motyl
Małgorzata Bulkowska
Karol Pawłowski
Magdalena Król
Karolina Romanowska
Elisabetta Manuali
Marta Pietrzak
Małgorzata Gajewska
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Tumor-associated macrophages; TAMs; Wnt pathway; cancer cells; metastasis
Affiliations: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland., Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland ; Department of Animal Environment Biology, Faculty of Animal Sciences, Warsaw University of Life Sciences, Warsaw, Poland., Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland ; Department of Large Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland., Area Diagnostica Integrata Istologia e Microscopia Elettronica Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, Perugia, Italy., Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Abstract:  Objective: According to the current hypothesis, tumor-associated macrophages (TAMs) are "corrupted" by cancer cells and subsequently facilitate, rather than inhibit, tumor metastasis. Because the molecular mechanisms of cancer cell-TAM interactions are complicated and controversial we aimed to better define this phenomenon. Methods and results: Using microRNA microarrays, Real-time qPCR and Western blot we showed that co-culture of canine mammary tumor cells with TAMs or treatment with macrophage-conditioned medium inhibited the canonical Wnt pathway and activated the non-canonical Wnt pathway in tumor cells. We also showed that co-culture of TAMs with tumor cells increased expression of canonical Wnt inhibitors in TAMs. Subsequently, we demonstrated macrophage-induced invasive growth patterns and epithelial-mesenchymal transition of tumor cells. Validation of these results in canine mammary carcinoma tissues (n = 50) and xenograft tumors indicated the activation of non-canonical and canonical Wnt pathways in metastatic tumors and non-metastatic malignancies, respectively. Activation of non-canonical Wnt pathway correlated with number of TAMs. Conclusions: We demonstrated that TAMs mediate a "switch" between canonical and non-canonical Wnt signaling pathways in canine mammary tumors, leading to increased tumor invasion and metastasis. Interestingly, similar changes in neoplastic cells were observed in the presence of macrophage-conditioned medium or live macrophages. These observations indicate that rather than being "corrupted" by cancer cells, TAMs constitutively secrete canonical Wnt inhibitors that decrease tumor proliferation and development, but as a side effect, they induce the non-canonical Wnt pathway, which leads to tumor metastasis. These data challenge the conventional understanding of TAM-cancer cell interactions. 

Retracted: Yes

PubPeer comments:
 This paper appears to duplicate heavily from a previously-published work by the same authors: Khanban, M. and Mahdikhani, M., 2018. The possible use of Sewage Sludge Ash (SSA) in Self-Consolidating Concrete (SCC) for environmental sustainability. Journal of Structural Engineering and Geo-Techniques, 8(1), pp.91-106. It is notable and disconcerting that certain results were reportedly identical between the two works (examples framed in blue below), whereas other results were reportedly different (examples framed in red below). It is not clear which results are the correct ones. ![file] ,