Macrophage-Colony-Stimulating Factor Receptor Enhances Prostate Cancer Cell Growth and Aggressiveness In Vitro and In Vivo and Increases Osteopontin Expression

Alexandra Mougel (1) , Eric Adriaenssens (2) , Boris Guyot (3) , Lu Tian (2) , Stéphanie Gobert (4) , Thierry Chassat (5) , Philippe Persoons (5) , David Hannebique (5) , Hélène Bauderlique-Le Roy (6) , Jérôme Vicogne (1) , Xuefen Le Bourhis (2) , Roland P Bourette (2)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
3 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
4 LBTI - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305
5 Institut Pasteur de Lille
6 PLBS - Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41

Prostate cancer is a major public health concern and one of the most prevalent forms of cancer worldwide. The definition of altered signaling pathways implicated in this complex disease is thus essential. In this context, abnormal expression of the receptor of Macrophage Colony-Stimulating Factor-1 (M-CSF or CSF-1) has been described in prostate cancer cells. Yet, outcomes of this expression remain unknown. Using mouse and human prostate cancer cell lines, this study has investigated the functionality of the wild-type CSF-1 receptor in prostate tumor cells and identified molecular mechanisms underlying its ligand-induced activation. Here, we showed that upon CSF-1 binding, the receptor autophosphorylates and activates multiple signaling pathways in prostate tumor cells. Biological experiments demonstrated that the CSF-1R/CSF-1 axis conferred significant advantages in cell growth and cell invasion in vitro. Mouse xenograft experiments showed that CSF-1R expression promoted the aggressiveness of prostate tumor cells. In particular, we demonstrated that the ligandactivated CSF-1R increased the expression of spp1 transcript encoding for osteopontin, a key player in cancer development and metastasis. Therefore, this study highlights that the CSF-1 receptor is fully functional in a prostate cancer cell and may be a potential therapeutic target for the treatment of prostate cancer.

Mots clés: Mougel; A. Adriaenssens; E. Guyot; B. Tian; L. Gobert; S. Chassat; T. Persoons; P. Hannebique; D. M-CSF CSF-1 receptor prostate C2H cell line TRAMP osteopontin SPP1 transcriptome; A.; Adriaenssens; E.; Guyot; B.; Tian; L.; Gobert; S.; Chassat; T.; Persoons; P.; Hannebique; D.; M-CSF; CSF-1 receptor; prostate; C2H cell line; TRAMP; osteopontin; SPP1; transcriptome

Domaines: Cancer

Alexandra Mougel, Eric Adriaenssens, Boris Guyot, Lu Tian, Stéphanie Gobert, et al.. Macrophage-Colony-Stimulating Factor Receptor Enhances Prostate Cancer Cell Growth and Aggressiveness In Vitro and In Vivo and Increases Osteopontin Expression. International Journal of Molecular Sciences, 2022, 23, ⟨10.3390/ijms232416028⟩. ⟨hal-04237745⟩