The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes
Copyright © 2024. Published by Elsevier B.V..
Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-β expression in nearby tumor cells. Then, TGF-β promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:588 |
|---|---|
| Enthalten in: |
Cancer letters - 588(2024) vom: 28. Apr., Seite 216769 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ye, Zeng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cell interaction |
|---|
| Anmerkungen: |
Date Completed 09.04.2024 Date Revised 09.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.canlet.2024.216769 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369279611 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369279611 | ||
| 003 | DE-627 | ||
| 005 | 20240409232535.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240305s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.canlet.2024.216769 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1370.xml |
| 035 | |a (DE-627)NLM369279611 | ||
| 035 | |a (NLM)38438098 | ||
| 035 | |a (PII)S0304-3835(24)00162-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ye, Zeng |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.04.2024 | ||
| 500 | |a Date Revised 09.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-β expression in nearby tumor cells. Then, TGF-β promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell interaction | |
| 650 | 4 | |a Spatial heterogeneity | |
| 650 | 4 | |a Tumor cell plasticity | |
| 650 | 4 | |a Tumor stroma | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Li, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yuheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Haifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Junfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Muzi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wuhu |e verfasserin |4 aut | |
| 700 | 1 | |a Lou, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Heli |e verfasserin |4 aut | |
| 700 | 1 | |a Jing, Desheng |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Guixiong |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xuemin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaowu |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xianjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Mingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Shunrong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer letters |d 1976 |g 588(2024) vom: 28. Apr., Seite 216769 |w (DE-627)NLM000147273 |x 1872-7980 |7 nnns |
| 773 | 1 | 8 | |g volume:588 |g year:2024 |g day:28 |g month:04 |g pages:216769 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.canlet.2024.216769 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 588 |j 2024 |b 28 |c 04 |h 216769 | ||