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TGF-β1-Induced Epithelial-Mesenchymal Transition Promotes Monocyte/Macrophage Properties in Breast Cancer Cells.

Johansson J, Tabor V, Wikell A, Jalkanen S, Fuxe J - Front Oncol (2015)

Bottom Line: However, in addition, we found another cluster of induced genes, which was specifically enriched in monocyte-derived macrophages, mast cells, and myeloid dendritic cells, but less in other types of immune cells.Further studies revealed that this monocyte/macrophage gene cluster was enriched in human breast cancer cell lines displaying an EMT or a Basal B profile, and in human breast tumors with EMT and undifferentiated (ER-/PR-) characteristics.The results identify an EMT-induced monocyte/macrophage gene cluster, which may play a role in breast cancer cell dissemination and metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institute , Stockholm , Sweden.

ABSTRACT
Breast cancer progression toward metastatic disease is linked to re-activation of epithelial-mesenchymal transition (EMT), a latent developmental process. Breast cancer cells undergoing EMT lose epithelial characteristics and gain the capacity to invade the surrounding tissue and migrate away from the primary tumor. However, less is known about the possible role of EMT in providing cancer cells with properties that allow them to traffic to distant sites. Given the fact that pro-metastatic cancer cells share a unique capacity with immune cells to traffic in-and-out of blood and lymphatic vessels we hypothesized that tumor cells undergoing EMT may acquire properties of immune cells. To study this, we performed gene-profiling analysis of mouse mammary EpRas tumor cells that had been allowed to adopt an EMT program after long-term treatment with TGF-β1 for 2 weeks. As expected, EMT cells acquired traits of mesenchymal cell differentiation and migration. However, in addition, we found another cluster of induced genes, which was specifically enriched in monocyte-derived macrophages, mast cells, and myeloid dendritic cells, but less in other types of immune cells. Further studies revealed that this monocyte/macrophage gene cluster was enriched in human breast cancer cell lines displaying an EMT or a Basal B profile, and in human breast tumors with EMT and undifferentiated (ER-/PR-) characteristics. The results identify an EMT-induced monocyte/macrophage gene cluster, which may play a role in breast cancer cell dissemination and metastasis.

No MeSH data available.


Related in: MedlinePlus

Gene expression profiling of long-term EMT cells. (A) Heat map showing genes significantly (P ≤ 0.05) upregulated (515 genes, upper part) or downregulated (463 genes, lower part) by >1.5-fold in long-term EMT vs. control EpRas cells. (B) Results from cluster analysis of genes significantly upregulated or downregulated in long-term EMT cells.
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Figure 2: Gene expression profiling of long-term EMT cells. (A) Heat map showing genes significantly (P ≤ 0.05) upregulated (515 genes, upper part) or downregulated (463 genes, lower part) by >1.5-fold in long-term EMT vs. control EpRas cells. (B) Results from cluster analysis of genes significantly upregulated or downregulated in long-term EMT cells.

Mentions: Microarray-based gene expression profiling of triplicate samples revealed that 515 genes were significantly upregulated, and 463 genes downregulated by more than 1.5-fold in long-term EMT cells compared to control cells (Figure 2A). The whole array set can be accessed at GEO database (Accession number: GSE59922). The 100 most upregulated and downregulated genes are displayed in Tables S1 and S2 in Supplementary Material). As expected, epithelial genes known to be inactivated during EMT in breast cancer cells, such as Cdh1 (E-cadherin), Ocln (Occludin), Epcam, Cldn7 (Claudin 7), Id1, Krt7, Esr1, Cav2, Dsp, Gata3, and Cadm1 were among the downregulated genes. Reciprocally, known EMT-related genes, such as Tnc, Mmp9, Jag1, Itgb3, Cdh5, Sema7a, Ctsw, and Itg5 were among the genes significantly upregulated in long-term EMT cells. Changes in the expression of several of these genes were validated by q-PCR (Figure S2A in Supplementary Material).


TGF-β1-Induced Epithelial-Mesenchymal Transition Promotes Monocyte/Macrophage Properties in Breast Cancer Cells.

Johansson J, Tabor V, Wikell A, Jalkanen S, Fuxe J - Front Oncol (2015)

Gene expression profiling of long-term EMT cells. (A) Heat map showing genes significantly (P ≤ 0.05) upregulated (515 genes, upper part) or downregulated (463 genes, lower part) by >1.5-fold in long-term EMT vs. control EpRas cells. (B) Results from cluster analysis of genes significantly upregulated or downregulated in long-term EMT cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306317&req=5

Figure 2: Gene expression profiling of long-term EMT cells. (A) Heat map showing genes significantly (P ≤ 0.05) upregulated (515 genes, upper part) or downregulated (463 genes, lower part) by >1.5-fold in long-term EMT vs. control EpRas cells. (B) Results from cluster analysis of genes significantly upregulated or downregulated in long-term EMT cells.
Mentions: Microarray-based gene expression profiling of triplicate samples revealed that 515 genes were significantly upregulated, and 463 genes downregulated by more than 1.5-fold in long-term EMT cells compared to control cells (Figure 2A). The whole array set can be accessed at GEO database (Accession number: GSE59922). The 100 most upregulated and downregulated genes are displayed in Tables S1 and S2 in Supplementary Material). As expected, epithelial genes known to be inactivated during EMT in breast cancer cells, such as Cdh1 (E-cadherin), Ocln (Occludin), Epcam, Cldn7 (Claudin 7), Id1, Krt7, Esr1, Cav2, Dsp, Gata3, and Cadm1 were among the downregulated genes. Reciprocally, known EMT-related genes, such as Tnc, Mmp9, Jag1, Itgb3, Cdh5, Sema7a, Ctsw, and Itg5 were among the genes significantly upregulated in long-term EMT cells. Changes in the expression of several of these genes were validated by q-PCR (Figure S2A in Supplementary Material).

Bottom Line: However, in addition, we found another cluster of induced genes, which was specifically enriched in monocyte-derived macrophages, mast cells, and myeloid dendritic cells, but less in other types of immune cells.Further studies revealed that this monocyte/macrophage gene cluster was enriched in human breast cancer cell lines displaying an EMT or a Basal B profile, and in human breast tumors with EMT and undifferentiated (ER-/PR-) characteristics.The results identify an EMT-induced monocyte/macrophage gene cluster, which may play a role in breast cancer cell dissemination and metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institute , Stockholm , Sweden.

ABSTRACT
Breast cancer progression toward metastatic disease is linked to re-activation of epithelial-mesenchymal transition (EMT), a latent developmental process. Breast cancer cells undergoing EMT lose epithelial characteristics and gain the capacity to invade the surrounding tissue and migrate away from the primary tumor. However, less is known about the possible role of EMT in providing cancer cells with properties that allow them to traffic to distant sites. Given the fact that pro-metastatic cancer cells share a unique capacity with immune cells to traffic in-and-out of blood and lymphatic vessels we hypothesized that tumor cells undergoing EMT may acquire properties of immune cells. To study this, we performed gene-profiling analysis of mouse mammary EpRas tumor cells that had been allowed to adopt an EMT program after long-term treatment with TGF-β1 for 2 weeks. As expected, EMT cells acquired traits of mesenchymal cell differentiation and migration. However, in addition, we found another cluster of induced genes, which was specifically enriched in monocyte-derived macrophages, mast cells, and myeloid dendritic cells, but less in other types of immune cells. Further studies revealed that this monocyte/macrophage gene cluster was enriched in human breast cancer cell lines displaying an EMT or a Basal B profile, and in human breast tumors with EMT and undifferentiated (ER-/PR-) characteristics. The results identify an EMT-induced monocyte/macrophage gene cluster, which may play a role in breast cancer cell dissemination and metastasis.

No MeSH data available.


Related in: MedlinePlus