Collagen in pituitary adenomas: A comprehensive review of biological roles and clinical implications

Pituitary adenomas (PAs) are common brain tumors, accounting for about 15% of all brain neoplasms. Although generally benign, they can lead to serious complications through mass effects and hormone dysregulation. Emerging evidence suggests that collagen, a major component of the extracellular matrix (ECM), plays a pivotal role in PA pathophysiology. Collagen provides both structural integrity and biochemical cues within the tumor microenvironment (TME), influencing cellular behaviors and intercellular interactions. Recent studies indicate that collagen remodeling in PAs is dynamic, with alterations in collagen composition and organization affecting tumor growth, invasion, and hormone secretion. Collagen degradation products and collagenase activity may also facilitate tumor invasion into adjacent tissues. Additionally, collagen has been implicated in immune modulation, acting as a physical barrier that restricts immune cell infiltration and promotes immune evasion through receptor-mediated signaling. Metabolically, collagen may serve as an energy source or modulate metabolic pathways to sustain tumor proliferation. Clinically, collagen content in PAs correlates with tumor consistency, which has implications for surgical resection strategies. Moreover, serum collagen is emerging as a potential non-invasive biomarker for PA diagnosis and prognosis. Targeting collagen synthesis, degradation, or its mechanotransductive signaling pathways represents a promising therapeutic avenue.