Ramy Gadalla1,2, Hebatallah Hassan3, Sherif Abdelaziz Ibrahim3, Mahmoud Salah Abdullah3, Ahmed Gaballah4, Burkhard Greve5, Somaya El-Deeb3, Mohamed El-Shinawi6, Mona Mostafa Mohamed3. 1. Department of Zoology, Faculty of Science, Cairo University, 12613, Giza, Egypt. ramy.gadalla@uhnresearch.ca. 2. Princess Margaret Cancer Center, University Health Network, 610 University Ave, Toronto, ON, M5G 2M9, Canada. ramy.gadalla@uhnresearch.ca. 3. Department of Zoology, Faculty of Science, Cairo University, 12613, Giza, Egypt. 4. Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. 5. Department of Radiotherapy-Radiooncology, University Hospital Münster, Münster, Germany. 6. Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract
PURPOSE: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis. METHODS: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancer patients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in human breast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR. RESULTS: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4+ cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression. CONCLUSIONS: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.
PURPOSE: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis. METHODS: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancerpatients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in humanbreast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR. RESULTS: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4+ cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression. CONCLUSIONS: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.
Entities:
Keywords:
Breast cancer; CXCR4; Lymph node metastasis; Plasmacytoid dendritic cells
Authors: Joanna Szpor; Joanna Streb; Anna Glajcar; Paulina Frączek; Aleksandra Winiarska; Katarzyna E Tyrak; Paweł Basta; Krzysztof Okoń; Robert Jach; Diana Hodorowicz-Zaniewska Journal: Diagnostics (Basel) Date: 2021-04-14
Authors: Crescenzo D'Alterio; Maria Buoncervello; Caterina Ieranò; Maria Napolitano; Luigi Portella; Giuseppina Rea; Antonio Barbieri; Antonio Luciano; Giosuè Scognamiglio; Fabiana Tatangelo; Anna Maria Anniciello; Mario Monaco; Ernesta Cavalcanti; Piera Maiolino; Giulia Romagnoli; Claudio Arra; Gerardo Botti; Lucia Gabriele; Stefania Scala Journal: J Exp Clin Cancer Res Date: 2019-10-28