APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer
| Autor: | Michael Hahne, Douglas Florindo-Pinheiro, Eva González-Suárez, Araceli García-Castro, Manuela Zonca, Burgo Gutiérrez del Burgo, Aránzazu García-Grande, Alex Cordero, Carla E. Carvalho-Pinto, Santos Mañes, Lourdes Planelles |
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| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Lung Neoplasms Transmembrane Activator and CAML Interactor Protein Blotting Western Tumor Necrosis Factor Ligand Superfamily Member 13 Fluorescent Antibody Technique Apoptosis Breast Neoplasms Mice Transgenic Biology medicine.disease_cause Real-Time Polymerase Chain Reaction Metastasis Immunoenzyme Techniques Paracrine signalling Mice Breast cancer medicine Biomarkers Tumor Tumor Cells Cultured Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger B-Cell Maturation Antigen Autocrine signalling Cell Proliferation Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction General Medicine medicine.disease Xenograft Model Antitumor Assays Carcinoma Basal Cell Cancer cell Female Breast carcinoma Carcinogenesis |
| Zdroj: | Carcinogenesis Carcinogenesis, Oxford University Press (OUP), 2015, 36 (5), pp.574--84. ⟨10.1093/carcin/bgv020⟩ |
| ISSN: | 0143-3334 1460-2180 |
| Popis: | APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL. The inflammatory stimulus poly I:C, a toll-like receptor (TLR) 3 ligand, enhanced APRIL secretion. Silencing experiments decreased cell proliferation, demonstrating that APRIL is a critical autocrine factor for breast tumor growth. Studies of 4T1 orthotopic breast tumors in APRIL transgenic mice showed that an APRIL-enriched environment increased tumor growth and promoted lung metastasis associated with enhanced tumor cell proliferation; BCMA and TACI expression suggests that both participate in these processes. We detected APRIL, BCMA and TACI in human luminal, triple-negative breast carcinomas and HER2 breast carcinomas, with increased levels in more aggressive basal tumors. APRIL was observed near Ki67(+) nuclei and was distributed heterogeneously in the cancer cells, in the leukocyte infiltrate, and in the myoepithelial layer adjacent to the tumor area; these results imply that APRIL provides proliferation signals to tumor cells through paracrine and autocrine signaling. Our study identifies participation of APRIL signaling in breast cancer promotion; we propose impairment of this pathway as a potential therapeutic strategy. |
| Databáze: | OpenAIRE |
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