Fibroblasts as Playmakers of Cancer Progression: Current Knowledge and Future Perspectives
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 25502
Special Issue Editor
Interests: tumor microenvironment; prostate cancer; pancreatic cancer; stromal paracrine signals; cancer-associated fibroblasts (CAFs); drug repositioning
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
In homeostatic epithelial–stromal interactions of adult tissues, stromal paracrine signals (morphogens) function to maintain the functional differentiation and growth/quiescence of epithelial cells. Once cancer cells grow in the epithelial compartment, the deregulation of homeostatic interactions occurs, leading to structural alterations of the stroma—so-called stromal remodeling. In contrast, the stroma-induced malignant transformation of epithelial cells is experimentally reported in prostate cancer development, suggesting that the structure of the stroma may play a critical role in cancer development and primary cancer cell progression.
In the tumor stroma of various solid tumors, invading cancer cells interact in complex ways with each other or with the surrounding microenvironment, generating the reactive stroma. The reactive stroma is composed mainly of cancer-promoting fibroblasts—so-called cancer-associated fibroblasts (CAFs). Within a focal lesion, CAFs heterotypically communicate with cancer cells not only by direct cell–cell contact via cell adhesion molecules but also by indirect cell–cell communication via mitogenic soluble factors, including growth factors, cytokines, extracellular matrix (ECM) molecules, and miRNAs. Interestingly, recent studies have unveiled that the reactive stroma of pancreatic cancer contains multiple functionally diverse populations of fibroblasts that positively or negatively regulate cancer progression (i.e., cancer-promoting or cancer-restraining).
In the tumor microenvironment, heterotypic interactions between cancer cells and fibroblasts must be quite important for determining cancer cell behavior, but we still know very little about the biological role of fibroblasts in the reactive stroma. In this Special Issue, we focus on heterotypic interactions between cancer cells and fibroblasts to develop an initial step toward designing reactive stroma-targeted therapies for the treatment of primary solid tumors. Impairing the malignant phenotype of cancer-promoting fibroblasts (e.g., via differentiation therapy targeting the reactive stroma) may abrogate primary cancer cell progression.
Dr. Kenichiro Ishii
Guest Editor
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Keywords
- tumor microenvironment
- reactive stroma
- fibroblasts
- cancer progression
- heterotypic interactions between cancer cells and fibroblasts
- reactive stroma-targeted therapy
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