title: Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy.
abstract: Mast cells affect growth in various human tumors, but their role in prostate cancer (PC) is unclear. Here, we identify mast cells as independent prognostic markers in PC using a large cohort of untreated PC patients with a long follow-up. By analyzing mast cells in different tissue compartments, our data indicate that intratumoral and peritumoral mast cells have anti- opposed to protumor properties. Intratumoral mast cells negatively regulate angiogenesis and tumor growth, whereas peritumoral mast cells stimulate the expansion of human prostate tumors. We also observed mast cell recruitment particularly to the peritumoral compartment in men during the formation of castrate-resistant prostate tumors. In our ortothopic rat model, mast cells accumulated in the peritumoral tissue where they enhanced angiogenesis and tumor growth. In line with this, prostate mast cells expressed high levels of the angiogenic factor FGF-2. Similar to the situation in men, mast cells infiltrated rat prostate tumors that relapsed after initially effective castration treatment, concurrent with a second wave of angiogenesis and an up-regulation of FGF-2. We conclude that mast cells are novel independent prognostic markers in PC and affect tumor progression in animals and patients. In addition, peritumoral mast cells provide FGF-2 to the tumor micro environment, which may contribute to their stimulating effect on angiogenesis.
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå, Sweden. ajohansson@waimr.uwa.edu.au
authors.forename: Anna
authors.initials: A
authors.lastname: Johansson
authors.forename: Stina
authors.initials: S
authors.lastname: Rudolfsson
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Sofia
authors.initials: S
authors.lastname: Halin
authors.forename: Kristian
authors.initials: K
authors.lastname: Pietras
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jones
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002369:Castration; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D016222:Fibroblast Growth Factor 2