Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer
Abstract Background Lymphatics provide a route for breast cancer cells to metastasize. Lymphatic endothelial cells (LECs), which form the structure of lymphatic vessels, play a key role in this process. Although LECs are pivotal in cancer progression, studies often rely on commercially available cel...
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BMC
2025-06-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-025-02067-w |
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| author | Asumi Iesato Jun Suzuka Kazutaka Otsuji Tomo Osako Nami Yamashita Yuka Inoue Tetsuyo Maeda Natsue Uehiro Kazuyo Yoshida Yoko Takahashi Kohei Kumegawa Sumito Saeki Liying Yang Ai Tsuchiya Kana Sakiyama Miwa Tanaka Takehiko Sakai Shinji Ohno Tetsuo Noda Takayuki Ueno Reo Maruyama |
| author_facet | Asumi Iesato Jun Suzuka Kazutaka Otsuji Tomo Osako Nami Yamashita Yuka Inoue Tetsuyo Maeda Natsue Uehiro Kazuyo Yoshida Yoko Takahashi Kohei Kumegawa Sumito Saeki Liying Yang Ai Tsuchiya Kana Sakiyama Miwa Tanaka Takehiko Sakai Shinji Ohno Tetsuo Noda Takayuki Ueno Reo Maruyama |
| author_sort | Asumi Iesato |
| collection | DOAJ |
| description | Abstract Background Lymphatics provide a route for breast cancer cells to metastasize. Lymphatic endothelial cells (LECs), which form the structure of lymphatic vessels, play a key role in this process. Although LECs are pivotal in cancer progression, studies often rely on commercially available cell lines that may not accurately reflect the tumor microenvironment. Therefore, there is a pressing need to directly study patient-derived LECs to better understand their role in breast cancer. Methods This study developed a method to isolate and characterize LECs directly from human breast-to-axilla adipose tissue. We used magnetic cell separation to remove CD45 + leukocytes and fluorescence-activated cell sorting to isolate cells expressing CD31 and podoplanin. Isolated cells were cultured under conditions promoting endothelial cell growth and were characterized through various assays assessing proliferation, tube formation, and gene expression patterns. Results The sorted CD31 + /PDPN + /CD45 − cell populations exhibited marked increases in proliferation upon VEGF-C stimulation and formed tubule structures on BME-coated dishes, confirming their LEC properties. Notably, isolated LECs showed distinct gene expression patterns depending on the presence of lymph node metastasis and lymphatic invasion. Conclusions The ability to isolate and characterize patient-derived LECs from mammary adipose tissue offers new insights into the cellular mechanisms underlying breast cancer metastasis. Significant gene expression variability related to disease state highlights the potential of these cells as biomarkers and therapeutic targets. This study emphasizes the importance of using patient-derived cells to accurately assess the tumor microenvironment, potentially leading to more personalized therapeutic approaches. |
| format | Article |
| id | doaj-art-c2bffb3ca99b4e99accec06e3481ca10 |
| institution | DOAJ |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-c2bffb3ca99b4e99accec06e3481ca102025-08-20T03:22:57ZengBMCBreast Cancer Research1465-542X2025-06-0127111210.1186/s13058-025-02067-wAxillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancerAsumi Iesato0Jun Suzuka1Kazutaka Otsuji2Tomo Osako3Nami Yamashita4Yuka Inoue5Tetsuyo Maeda6Natsue Uehiro7Kazuyo Yoshida8Yoko Takahashi9Kohei Kumegawa10Sumito Saeki11Liying Yang12Ai Tsuchiya13Kana Sakiyama14Miwa Tanaka15Takehiko Sakai16Shinji Ohno17Tetsuo Noda18Takayuki Ueno19Reo Maruyama20NEXT-Ganken Program, Cancer Cell Diversity Project, Japanese Foundation for Cancer ResearchNEXT-Ganken Program, Cancer Cell Diversity Project, Japanese Foundation for Cancer ResearchNEXT-Ganken Program, Cancer Cell Diversity Project, Japanese Foundation for Cancer ResearchDivision of Pathology, Cancer Institute, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchNEXT-Ganken Program, Cancer Cell Diversity Project, Japanese Foundation for Cancer ResearchDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer ResearchDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer ResearchDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer ResearchDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer ResearchDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchDirector’s Room, Cancer Institute, Japanese Foundation for Cancer ResearchBreast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchNEXT-Ganken Program, Cancer Cell Diversity Project, Japanese Foundation for Cancer ResearchAbstract Background Lymphatics provide a route for breast cancer cells to metastasize. Lymphatic endothelial cells (LECs), which form the structure of lymphatic vessels, play a key role in this process. Although LECs are pivotal in cancer progression, studies often rely on commercially available cell lines that may not accurately reflect the tumor microenvironment. Therefore, there is a pressing need to directly study patient-derived LECs to better understand their role in breast cancer. Methods This study developed a method to isolate and characterize LECs directly from human breast-to-axilla adipose tissue. We used magnetic cell separation to remove CD45 + leukocytes and fluorescence-activated cell sorting to isolate cells expressing CD31 and podoplanin. Isolated cells were cultured under conditions promoting endothelial cell growth and were characterized through various assays assessing proliferation, tube formation, and gene expression patterns. Results The sorted CD31 + /PDPN + /CD45 − cell populations exhibited marked increases in proliferation upon VEGF-C stimulation and formed tubule structures on BME-coated dishes, confirming their LEC properties. Notably, isolated LECs showed distinct gene expression patterns depending on the presence of lymph node metastasis and lymphatic invasion. Conclusions The ability to isolate and characterize patient-derived LECs from mammary adipose tissue offers new insights into the cellular mechanisms underlying breast cancer metastasis. Significant gene expression variability related to disease state highlights the potential of these cells as biomarkers and therapeutic targets. This study emphasizes the importance of using patient-derived cells to accurately assess the tumor microenvironment, potentially leading to more personalized therapeutic approaches.https://doi.org/10.1186/s13058-025-02067-wLymphatic endothelial cellsBreast cancerCell isolationLymphatic invasionGene expression analysis |
| spellingShingle | Asumi Iesato Jun Suzuka Kazutaka Otsuji Tomo Osako Nami Yamashita Yuka Inoue Tetsuyo Maeda Natsue Uehiro Kazuyo Yoshida Yoko Takahashi Kohei Kumegawa Sumito Saeki Liying Yang Ai Tsuchiya Kana Sakiyama Miwa Tanaka Takehiko Sakai Shinji Ohno Tetsuo Noda Takayuki Ueno Reo Maruyama Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer Breast Cancer Research Lymphatic endothelial cells Breast cancer Cell isolation Lymphatic invasion Gene expression analysis |
| title | Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| title_full | Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| title_fullStr | Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| title_full_unstemmed | Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| title_short | Axillary adipose tissue–derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| title_sort | axillary adipose tissue derived lymphatic endothelial cells exhibit distinct transcriptomic signatures reflecting lymphatic invasion status in breast cancer |
| topic | Lymphatic endothelial cells Breast cancer Cell isolation Lymphatic invasion Gene expression analysis |
| url | https://doi.org/10.1186/s13058-025-02067-w |
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