Cancer Growth and Invasion Are Increased in the Tight Skin (TSK) Mouse.

Area of Science:

• Oncology
• Immunology
• Rheumatology

Background:

• Systemic sclerosis (SSc) patients have higher solid malignancy risks.
• The underlying mechanisms linking SSc and cancer remain unclear.
• The tight skin (TSK) mouse model mimics SSc pathologies but its cancer modeling potential is unexplored.

Purpose of the Study:

• To investigate the TSK mouse model's utility in studying cancer progression.
• To determine if the altered TSK microenvironment influences tumor formation and invasiveness.
• To identify specific microenvironmental changes in TSK mice that promote cancer.

Main Methods:

• Compared tumor formation in TSK and wild-type (WT) mice using syngeneic breast, melanoma, and ovarian cancer cell lines.
• Utilized subcutaneous and intraperitoneal tumor implantation models.
• Employed bulk and single-cell RNA sequencing to analyze tumor and microenvironment characteristics.

Main Results:

• TSK mice consistently developed more invasive subcutaneous tumors across all cancer types.
• Ovarian tumors in TSK mice also showed heightened invasiveness in the peritoneal cavity.
• TSK tumors exhibited increased neutrophil-to-lymphocyte ratio and profibrotic myofibroblast/macrophage populations.

Conclusions:

• The TSK mouse is a valuable preclinical model for SSc-associated cancer research.
• The SSc-like microenvironment in TSK mice actively promotes tumor invasion and progression.
• Specific immune and fibrotic alterations in TSK mice contribute to a pro-tumorigenic environment.