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Series GSE62598 Query DataSets for GSE62598
Status Public on Mar 20, 2015
Title Granulocytic immune infiltrates are essential for the efficient formation of breast cancer liver metastases
Organism Mus musculus
Experiment type Expression profiling by array
Summary Breast cancer cells display preferences for specific metastatic sites including the bone, lung and liver. Metastasis is a complex process that relies, in part, on interactions between disseminated cancer cells and resident/infiltrating stromal cells that constitute the metastatic microenvironment. Distinct immune infiltrates can either impair the metastatic process or conversely, assist in the seeding, colonization and growth of disseminated cancer cells. Using in vivo selection approaches, we previously isolated 4T1-derived breast cancer cells that preferentially metastasize to these organs and tissues. In this study, we examined whether the propensity of breast cancer cells to metastasize to the lung, liver or bone is associated with and dependent on distinct patterns of immune cell infiltration. Immunohistocytochemistry and immunohistofluorescence approaches were used to quantify granulocytic infiltrates within distinct metastases and depletion of Gr1+ cells was performed to functionally interrogate the role of myeloid/granulocytic infiltrates in promoting metastasis to these organs.
We show that T lymphocytes (CD3+), myeloid-derived/granulocytic cells (Gr-1+) cells and neutrophils (NE+) exhibit the most pronounced recruitment in lung and liver metastases, with markedly less recruitment within bone metastatic lesions. Interestingly, these infiltrating cell populations display different patterns of localization within soft tissue metastases. T lymphocytes and neutrophils are localized around the periphery of liver metastases whereas they were dispersed throughout the lung metastases. Furthermore, Gr-1+ cell-depletion studies demonstrate that infiltrating myeloid-derived/granulocytic cells, including neutrophils, are essential for the formation of breast cancer liver metastases but dispensable for metastasis to the lung and bone. Finally, we demonstrate that neutrophils that infiltrate and surround the liver metastases are polarized towards an N2 phenotype, which have previously been shown to enhance tumor growth and metastasis. Our results demonstrate that the liver metastatic potential of breast cancer cells is heavily reliant on interactions with infiltrating myeloid/granulocytic cells in the liver microenvironment.
Overall design Gene expression profile comparison from 4T1 parental and individual in vivo selected metastatic sub-populations.
Contributor(s) Siegel PM, Tabariès S, Ouellet V
Citation(s) 25882816
Submission date Oct 22, 2014
Last update date Jan 12, 2017
Contact name Peter M Siegel
Organization name McGill University
Department Medicine
Lab Room 513
Street address 1160 Pine avenue West
City Montreal
State/province Quebec
ZIP/Postal code H3A 1A3
Country Canada
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (15)
GSM1529765 4T1 parental rep D
GSM1529766 4T1 parental rep E
GSM1529767 4T1 parental rep F
BioProject PRJNA264523

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Supplementary file Size Download File type/resource
GSE62598_RAW.tar 239.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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