title: Hematogenic Dissemination of Triple-negative Versus Hormonal Receptor-positive Breast Cancer Cells.
abstract: The aim of this study was to characterize the hematogeneous spread, in vivo, of breast cancer (BC) cell lines that express hormonal receptors (HR) comparing with triple-negative (TN) BC, particularly considering the lung and liver. Female Balb/c nu nu mice (n=30) were injected with two breast cancer cell lines (MCF7 and HCC1806). Nuclear medicine imaging with Technetium ((99m)Tc)-hydroxymethylene diphosphonate ((99m)Tc-HMDP) and (99m)Tc-Hexakis 2-methoxy-2-methylpropylisonitrile (MIBI) were performed between the 7th and 8th weeks after injection. The histological metastatic foci were analyzed by morphometric and immunohistochemistry studies regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (ERBB2) and cytokeratin (CK)-5/6. The mean area of lung metastasis in MCF7 cases was significantly higher (p=0.023), although the number of liver foci was higher in the HCC1806 group (p=0.006). Logistic regression revealed a potentiating model for liver metastasis with HCC1806 cells (odds ratio=16; p=0.03). The number and area of lung-metastatic foci were not predictive of liver dissemination. Lung metastasis study showed ER positivity in 57.1% of the MCF7 group, compared to 80% of the HCC1806 group. PR was positive in 42.9% of MCF7 cases and negative in 60% of HCC1806 cases. HR-positive cells developed massive lung metastization. TN cells seem to potentiate liver metastasis. ER, PR, ERBB2 and basal-like CK expression in metastases was not uniformly correlated with that of primary tumor cells.
authors.affiliation: Gynecology A Service, Coimbra Hospital and Universitary Center, Coimbra, Portugal Biophysics Unit - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal Centre of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine of Coimbra University, Coimbra, Portugal mariaj.carvalho@sapo.pt.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Carvalho
authors.affiliation: Biophysics Unit - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal Centre of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine of Coimbra University, Coimbra, Portugal Neurosciences Institute, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Abrantes
authors.affiliation: Biophysics Unit - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal Centre of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine of Coimbra University, Coimbra, Portugal Neurosciences Institute, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Laranjo
authors.affiliation: Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Gynecology A Service, Coimbra Hospital and Universitary Center, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Torgal
authors.affiliation: Experimental Pathology Institute, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: António Silvério
authors.initials: AS
authors.lastname: Cabrita
authors.affiliation: Biophysics Unit - Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal Centre of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine of Coimbra University, Coimbra, Portugal Neurosciences Institute, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: Filomena
authors.initials: F
authors.lastname: Botelho
authors.affiliation: Centre of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine of Coimbra University, Coimbra, Portugal.
authors.forename: Carlos Freire
authors.initials: CF
authors.lastname: DE Oliveira
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary; D008175:Lung Neoplasms / Q000175:diagnosis / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Breast cancer; animal model of dissemination; metastasis