title: Comparison of the Adipose and Luminal Mammary Gland Compartment as Orthotopic Inoculation Sites in a 4T1-Based Immunocompetent Preclinical Model for Triple-Negative Breast Cancer.
abstract: Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice. Following tumor cell inoculation in the adipose compartment of non-pretreated/naive, hormonally pretreated/naive and non-pretreated/lactating mice, the primary tumors developed similarly. However, a slower onset of primary tumor growth was found after inoculations in the luminal compartment of non-pretreated/lactating mice. Despite this difference in tumor development rate, metastasis to the liver and lungs was equally observed and was accompanied by lymphatic spreading of tumor cells and progressive splenomegaly with both inoculation types. Chitinase 3-like 1 (CHI3L1) and lipocalin 2 (LCN2) served as innovative biomarkers for disease progression showing increased levels in primary tumors and sera of the non-pretreated/lactating inoculation groups. A slower increase in circulating CHI3L1 but not LCN2 levels, was observed after inoculations in the luminal compartment which corroborated the slower tumor development at this inoculation site. Our results highlight the critical impact of different mammary gland compartments on tumor development in syngeneic murine models and support the use of novel tumor progression biomarkers in an immune-competent environment.
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Jonas.Steenbrugge@UGent.be.|Translational Cancer Research Unit Antwerp, Center for Oncological Research, General Hospital Sint-Augustinus, Wilrijk, Belgium. Jonas.Steenbrugge@UGent.be.
authors.forename: Jonas
authors.identifier: 0000-0002-7763-2888
authors.initials: J
authors.lastname: Steenbrugge
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Breyne
authors.affiliation: Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Denies
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.|Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dekimpe
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Demeyere
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research, Laboratory of Experimental Cancer Research, Ghent University, Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Translational Cancer Research Unit Antwerp, Center for Oncological Research, General Hospital Sint-Augustinus, Wilrijk, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vermeulen
authors.affiliation: Translational Cancer Research Unit Antwerp, Center for Oncological Research, General Hospital Sint-Augustinus, Wilrijk, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Van Laere
authors.affiliation: Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Niek N
authors.initials: NN
authors.lastname: Sanders
authors.affiliation: Laboratory of Biochemistry, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Meyer
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007774:Lactation / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: 4T1 immunocompetent preclinical model; Adipose and luminal compartment; Chitinase 3-like 1; Lipocalin 2; Orthotopic inoculation; Triple-negative breast cancer