TY - JOUR
T1 - Cancer-associated fibroblasts that restrain cancer progression
T2 - Hypotheses and perspectives
AU - Miyai, Yuki
AU - Esaki, Nobutoshi
AU - Takahashi, Masahide
AU - Enomoto, Atsushi
N1 - Funding Information:
We thank all the colleagues involved in the current research projects in our laboratory. We are grateful to Genichiro Ishii (National Cancer Center), Akira Orimo (Juntendo University) and Kenichiro Ishii (Mie University) for helpful discussions. This work was supported by: a Grant-in-Aid for Scientific Research (S) (26221304 to MT) and a Grant-in-Aid for Scientific Research (B) (18H02638 to AE) commissioned by the Ministry of Education, Culture, Sports, Science and Technology of Japan; AMED-CREST (Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology; 19gm0810007h0104 and 19gm1210008s0101 to AE); and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED (19cm0106332h0002 to AE).
PY - 2020/4/1
Y1 - 2020/4/1
N2 - The roles of cancer-associated fibroblasts (CAF) in the progression of various types of cancers are well established. CAF promote cancer progression through pleiotropic mechanisms, including the secretion of soluble factors and extracellular matrix, physical interactions with cancer cells, and the regulation of angiogenesis, immunity and metabolism. Their contribution to therapeutic resistance is also well appreciated. Therefore, CAF have been considered as a therapeutic target in cancer. However, recent studies in autochthonous pancreatic cancer models suggest that specific subset(s) of CAF exhibit cancer-restraining roles, indicating that CAF are functionally and molecularly heterogeneous, which is supported by recent single-cell transcriptome analyses. While cancer-promoting CAF (pCAF) have been extensively studied, the nature and specific marker(s) of cancer-restraining CAF (rCAF) have remained uncharacterized. Interestingly, a recent study provided insight into the nature of rCAF and suggested that they may share molecular properties with pancreatic stellate cells (PSC) and mesenchymal stem/stromal cells (MSC). Complicating this finding is that PSC and MSC have been shown to promote the formation of a tumor-permissive and tumor-promoting environment in xenograft tumor models. However, these cells undergo significant transcriptional and epigenetic changes during ex vivo culture, which confounds the interpretation of experimental results based on the use of cultured cells. In this short review, we describe recent studies and hypotheses on the identity of rCAF and discuss their analogy to fibroblasts that suppress fibrosis in fibrotic diseases. Finally, we discuss how these findings can be exploited to develop novel anticancer therapies in the future.
AB - The roles of cancer-associated fibroblasts (CAF) in the progression of various types of cancers are well established. CAF promote cancer progression through pleiotropic mechanisms, including the secretion of soluble factors and extracellular matrix, physical interactions with cancer cells, and the regulation of angiogenesis, immunity and metabolism. Their contribution to therapeutic resistance is also well appreciated. Therefore, CAF have been considered as a therapeutic target in cancer. However, recent studies in autochthonous pancreatic cancer models suggest that specific subset(s) of CAF exhibit cancer-restraining roles, indicating that CAF are functionally and molecularly heterogeneous, which is supported by recent single-cell transcriptome analyses. While cancer-promoting CAF (pCAF) have been extensively studied, the nature and specific marker(s) of cancer-restraining CAF (rCAF) have remained uncharacterized. Interestingly, a recent study provided insight into the nature of rCAF and suggested that they may share molecular properties with pancreatic stellate cells (PSC) and mesenchymal stem/stromal cells (MSC). Complicating this finding is that PSC and MSC have been shown to promote the formation of a tumor-permissive and tumor-promoting environment in xenograft tumor models. However, these cells undergo significant transcriptional and epigenetic changes during ex vivo culture, which confounds the interpretation of experimental results based on the use of cultured cells. In this short review, we describe recent studies and hypotheses on the identity of rCAF and discuss their analogy to fibroblasts that suppress fibrosis in fibrotic diseases. Finally, we discuss how these findings can be exploited to develop novel anticancer therapies in the future.
UR - http://www.scopus.com/inward/record.url?scp=85081206926&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081206926&partnerID=8YFLogxK
U2 - 10.1111/cas.14346
DO - 10.1111/cas.14346
M3 - Review article
C2 - 32060987
AN - SCOPUS:85081206926
VL - 111
SP - 1047
EP - 1057
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 4
ER -