Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion
Carcinoma-associated fibroblasts (CAFs) are abundant stromal cells in tumor microenvironment that are critically involved in cancer progression. Contrasting reports have shown that CAFs can have either pro- or antitumorigenic roles, indicating that CAFs are functionally heterogeneous. Therefore, to...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618305748 |
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doaj-dee2915adb844c6bb8509c156a0669fc |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jing Hao Cédric Zeltz Melania Pintilie Quan Li Shingo Sakashita Tao Wang Michael Cabanero Sebastiao N. Martins-Filho Dennis Y. Wang Elena Pasko Kalpana Venkat Joella Joseph Vibha Raghavan Chang-Qi Zhu Yu-Hui Wang Nadeem Moghal Ming-Sound Tsao Roya Navab |
| spellingShingle |
Jing Hao Cédric Zeltz Melania Pintilie Quan Li Shingo Sakashita Tao Wang Michael Cabanero Sebastiao N. Martins-Filho Dennis Y. Wang Elena Pasko Kalpana Venkat Joella Joseph Vibha Raghavan Chang-Qi Zhu Yu-Hui Wang Nadeem Moghal Ming-Sound Tsao Roya Navab Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion Neoplasia: An International Journal for Oncology Research |
| author_facet |
Jing Hao Cédric Zeltz Melania Pintilie Quan Li Shingo Sakashita Tao Wang Michael Cabanero Sebastiao N. Martins-Filho Dennis Y. Wang Elena Pasko Kalpana Venkat Joella Joseph Vibha Raghavan Chang-Qi Zhu Yu-Hui Wang Nadeem Moghal Ming-Sound Tsao Roya Navab |
| author_sort |
Jing Hao |
| title |
Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion |
| title_short |
Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion |
| title_full |
Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion |
| title_fullStr |
Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion |
| title_full_unstemmed |
Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell Invasion |
| title_sort |
characterization of distinct populations of carcinoma-associated fibroblasts from non–small cell lung carcinoma reveals a role for st8sia2 in cancer cell invasion |
| publisher |
Elsevier |
| series |
Neoplasia: An International Journal for Oncology Research |
| issn |
1476-5586 |
| publishDate |
2019-05-01 |
| description |
Carcinoma-associated fibroblasts (CAFs) are abundant stromal cells in tumor microenvironment that are critically involved in cancer progression. Contrasting reports have shown that CAFs can have either pro- or antitumorigenic roles, indicating that CAFs are functionally heterogeneous. Therefore, to precisely target the cancer-promoting CAF subsets, it is necessary to identify specific markers to define these subpopulations and understand their functions. We characterized two CAFs subsets from 28 non–small cell lung cancer (NSCLC) patient tumors that were scored and classified based on desmoplasia [mainly characterized by proliferating CAFs; high desmoplastic CAFs (HD-CAF; n = 15) and low desmoplastic CAFs (LD-CAF; n = 13)], which is an independent prognostic factor. Here, for the first time, we demonstrate that HD-CAFs and LD-CAFs show different tumor-promoting abilities. HD-CAFs showed higher rate of collagen matrix remodeling, invasion, and tumor growth compared to LD-CAFs. Transcriptomic analysis identified 13 genes that were differentially significant (fold ≥1.5; adjusted P value < .1) between HD-CAFs and LD-CAFs. The top upregulated differentially expressed gene, ST8SIA2 (11.3 fold; adjusted P value = .02), enhanced NSCLC tumor cell invasion in 3D culture compared to control when it was overexpressed in CAFs, suggesting an important role of ST8SIA2 in cancer cell invasion. We confirmed the protumorigenic role of ST8SIA2, showing that ST8SIA2 was significantly associated with the risk of relapse in three independent NSCLC clinical datasets. In summary, our studies show that functional heterogeneity in CAF plays key role in promoting cancer cell invasion in NSCLC. |
| url |
http://www.sciencedirect.com/science/article/pii/S1476558618305748 |
| work_keys_str_mv |
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doaj-dee2915adb844c6bb8509c156a0669fc2020-11-25T00:53:13ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-05-01215482493Characterization of Distinct Populations of Carcinoma-Associated Fibroblasts from Non–Small Cell Lung Carcinoma Reveals a Role for ST8SIA2 in Cancer Cell InvasionJing Hao0Cédric Zeltz1Melania Pintilie2Quan Li3Shingo Sakashita4Tao Wang5Michael Cabanero6Sebastiao N. Martins-Filho7Dennis Y. Wang8Elena Pasko9Kalpana Venkat10Joella Joseph11Vibha Raghavan12Chang-Qi Zhu13Yu-Hui Wang14Nadeem Moghal15Ming-Sound Tsao16Roya Navab17Cancer Center, Qilu Hospital of Shandong University, Jinan, ChinaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaSheffield Institute of Translational Neuroscience, University of Sheffield, Sheffield, UK, S1O 2HQPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Departments of Medical Biophysics, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Departments of Medical Biophysics, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada; Departments of Medical Biophysics, Toronto, Ontario, Canada; Ontario Institute of Cancer Research, Toronto, Ontario, CanadaPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada; Address all correspondence to: Roya Navab, Princess Margaret Cancer Research Tower / University Health Network, 101 College St. 11th Floor / Rm 11-301AM, Toronto, ON, M5G 1L7.Carcinoma-associated fibroblasts (CAFs) are abundant stromal cells in tumor microenvironment that are critically involved in cancer progression. Contrasting reports have shown that CAFs can have either pro- or antitumorigenic roles, indicating that CAFs are functionally heterogeneous. Therefore, to precisely target the cancer-promoting CAF subsets, it is necessary to identify specific markers to define these subpopulations and understand their functions. We characterized two CAFs subsets from 28 non–small cell lung cancer (NSCLC) patient tumors that were scored and classified based on desmoplasia [mainly characterized by proliferating CAFs; high desmoplastic CAFs (HD-CAF; n = 15) and low desmoplastic CAFs (LD-CAF; n = 13)], which is an independent prognostic factor. Here, for the first time, we demonstrate that HD-CAFs and LD-CAFs show different tumor-promoting abilities. HD-CAFs showed higher rate of collagen matrix remodeling, invasion, and tumor growth compared to LD-CAFs. Transcriptomic analysis identified 13 genes that were differentially significant (fold ≥1.5; adjusted P value < .1) between HD-CAFs and LD-CAFs. The top upregulated differentially expressed gene, ST8SIA2 (11.3 fold; adjusted P value = .02), enhanced NSCLC tumor cell invasion in 3D culture compared to control when it was overexpressed in CAFs, suggesting an important role of ST8SIA2 in cancer cell invasion. We confirmed the protumorigenic role of ST8SIA2, showing that ST8SIA2 was significantly associated with the risk of relapse in three independent NSCLC clinical datasets. In summary, our studies show that functional heterogeneity in CAF plays key role in promoting cancer cell invasion in NSCLC.http://www.sciencedirect.com/science/article/pii/S1476558618305748 |