Stromal KITL/SCF Maintains Pancreas Tissue Homeostasis and Restrains Tumor Progression

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Abstract Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and nonimmune stromal elements enable loss of homeostasis during tumor onset. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. In this study, we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify the loss of stromal KITL during tumorigenesis as tumor promoting. Genetic inhibition of mesenchymal KITL in the contexts of health, injury, and cancer together indicates a role for KITL signaling in the maintenance of pancreas tissue architecture, such that the loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate the loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment. Significance By analyzing transcriptional programs in healthy and tumor-associated pancreatic mesenchyme, we find that a subpopulation of mesenchymal cells in healthy pancreas tissue expresses the paracrine signaling factor KITL. The loss of mesenchymal KITL is an accompanying and permissive feature

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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