Pancreatic ductal adenocarcinoma (PDAC) possesses a dense and fibrotic desmoplastic stroma. The pancreatic tumor microenvironment (TME) mainly consists of extracellular matrix, resident and recruited cells, and cancer-associated fibroblasts (CAFs), which play a crucial role in tumor progression and metastasis, metabolism, angiogenesis, and treatment resistance (such as immunosuppression and chemoresistance). Among them, CAFs are key components of the pancreatic TME. In addition to maintaining the extracellular matrix, CAFs are also involved in complex crosstalk with infiltrating immunocytes and PC cells. Thus, CAFs serve as potential targets for the development of PDAC therapeutic strategies.
Fig.1 Impact of CAFs on major hallmarks of PC. (Sun, Qiqing, et al., 2018)
Overview of PC fibroblast
CAFs are characterized by tissue-resident, spindle-shaped, originating from different pancreatic cell types, including resident fibroblasts (the most prominent source), pancreatic stellate cells (PSCs), bone marrow-derived cells (BMDCs), and epithelial cells. As the major non-neoplastic component of pancreatic TME, CAFs not only promote the formation of the desmoplastic stroma by secreting extracellular matrix proteins but also regulate cancer progression by influencing cytokines/chemokine production. In addition, CAFs have also been reported to play an integral role in treatment resistance, including immunosuppression and chemoresistance. All these factors make CAFs potential therapeutic targets for treating PC.
Fig. 2 Heterogeneous origins and activation of CAFs. (Sun, Qiqing, et al., 2018)
The service offering at Alfa Cytology
Alfa Cytology is a leading global life sciences company. We have an in-depth understanding of PC cells and other components. Here, we offer different preclinical models of pancreatic CAFs to help our global customers develop successful CAF-targeted therapeutic regimens. In addition to these preclinical models of pancreatic CAFs, we also offer the following services, but are not limited to:
- Isolation and culture of pancreatic CAFs.
- Characterization of pancreatic CAFs. CAFs can be characterized by immunohistochemical staining with vimentin-rabbit polyclonal IgG antibody, monoclonal mouse anti-glial fibrillary acidic protein (GFAP) antibody, and monoclonal mouse anti-actin α-smooth muscle (α-SMA) antibody.
- Functional analysis of pancreatic CAFs, such as the migration capacity of fibroblasts
| Preclinical models of pancreatic CAFs | ||
|---|---|---|
| Models | Applications | Advantages |
| 2D cell coculture | -Analysis of the interaction between CAFs and PC cells -Analysis of signaling pathway |
-Low cost and time benefit -Flexible cultural conditions |
| 3D organoids | -Analysis of the interaction between CAFs and other cells -Investigation of early events in tumor progression, cell invasion and migration |
-Optional and quantitative model components |
| Cell line-derived coinjection xenografts | -Study of fibrosis, tumor growth, metastasis, and angiogenesis -Drug development |
-Moderate cost and time benefit |
| Genetically engineered mouse models |
-Genetic analysis of CAFs on tumor progression -TME and immune monitoring -Drug screening |
-Intact immune system -Closely mimics human cancer |
Applications of our services
The important and diverse functions of CAFs in pancreatic TME make them ideal targets for PC therapy. Significant efforts have been made in both preclinical studies and clinical trials, with varying degrees of success. Our services are available to advance preclinical studies primarily targeting CAFs, specifically:
- Depletion of CAFs in the TME
- Targeting extracellular matrix (ECM) production by CAFs
- Targeting metabolic pathways in CAFs
- Targeting CAF-induced immunosuppression
- Modulating CAF phenotype in the TME
Whatever the size and complexity of your project, please contact us for a professional, competitively priced solution that fits your needs.
References
- Sun, Qiqing, et al. "The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer." Theranostics 8.18 (2018): 5072.
- Vaish, Utpreksha, et al. "Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma: An Update on Heterogeneity and Therapeutic Targeting." International journal of molecular sciences 22.24 (2021): 13408.