A clinically relevant bi-cellular murine mammary tumor model as a useful tool for evaluating the effect of retinoic acid signaling on tumor progression

Autor: María José Veloso, Elisa Bal de Kier Joffé, Eduardo F. Farias, Lydia Puricelli, Paola B. Campodónico, Laura B. Todaro
Rok vydání: 2011
Předmět:
Receptors
Retinoic Acid
Cell
Retinoic acid
Ciencias de la Salud
Fluorescent Antibody Technique
Apoptosis
Immunoenzyme Techniques
chemistry.chemical_compound
Mice
Cell Movement
Tumor Cells
Cultured
Pharmacology (medical)
Retinoid
Mammary tumor
Mice
Inbred BALB C
Reverse Transcriptase Polymerase Chain Reaction
General Medicine
Cell cycle
Flow Cytometry
Otras Ciencias de la Salud
medicine.anatomical_structure
Oncology
Female
Signal Transduction
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
medicine.drug_class
Blotting
Western
Mitosis
Mammary Neoplasms
Animal
Biology
Adenocarcinoma
Real-Time Polymerase Chain Reaction
Retinoids
BREAST CANCER
Internal medicine
medicine
Cell Adhesion
Animals
Radiology
Nuclear Medicine and imaging
RNA
Messenger
Cell Proliferation
Cell growth
Epithelial Cells
Urokinase-Type Plasminogen Activator
Matrix Metalloproteinases
LUMINAL AND MYOEPITHELIAL CELLS
Disease Models
Animal
Endocrinology
chemistry
Cell culture
Tumor progression
METASTASIS
Cancer research
RETINOIDS
Zdroj: Breast cancer (Tokyo, Japan). 20(4)
ISSN: 1880-4233
Popis: BACKGROUND: The effect of retinoic acid (RA) on breast cancer progression is controversial. Our objective was to obtain information about breast cancer progression, taking advantage of the ER-negative murine mammary adenocarcinoma model LM38 (LM38-LP constituted by luminal (LEP) and myoepithelial-like cells (MEP), LM38-HP mainly composed of spindle-shaped epithelial cells, and LM38-D2 containing only large myoepithelial cells), and to validate the role of the retinoic acid receptors (RARs) in each cell-type compartment. MATERIALS AND METHODS: We studied the expression and functionality of the RARs in LM38 cell lines. We analyzed cell growth and cell cycle distribution, apoptosis, the activity of proteases, motility properties, and expression of the molecules involved in these pathways. We also evaluated tumor growth and dissemination in vivo under retinoid treatment. RESULTS: LM38 cell lines expressed most retinoic receptor isotypes that were functional. However, only the bi-cellular LM38-LP cells responded to retinoids by increasing RARβ2 and CRBP1 expression. The growth of LM38 cell sublines was inhibited by retinoids, first by inducing arrest in MEP cells, then apoptosis in LEP cells. Retinoids induced inhibitory effects on motility, invasiveness, and activity of proteolytic enzymes, mainly in the LM38-LP cell line. In in-vivo assays with the LM38-LP cell line, RA treatment impaired both primary tumor growth and lung metastases dissemination. CCONCLUSION: These in-vivo and in-vitro results show that to achieve maximum effects of RA on tumor progression both the LEP and MEP cell compartments have to be present, suggesting that the interaction between the LEP and MEP cells is crucial to full activation of the RARs. Fil: Todaro, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina Fil: Veloso, María José. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina Fil: Campodónico, Paola Bernadette. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina Fil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina Fil: Farias, Eduardo Francisco. Mount Sinai School of Medicine; Estados Unidos Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
Databáze: OpenAIRE
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