E22 Host tissue and extracellular matrix

Topic

A tumor does not grow in a vacuum; it grows within host tissue that possesses its own mechanical and biochemical properties—centered largely on the extracellular matrix surrounding the cells—characterized by specific stiffness and composition.

The tumor does not merely grow within this extracellular matrix; it actively remodels it, altering its stiffness and composition to facilitate its own invasion of the host tissue and its own growth.

This extracellular matrix is ​​not simply a passive scaffold that the tumor traverses; it is an active regulator of tumor biology. Its stiffness modulates the mechanical signaling received by tumor cells, and this signaling, in turn, promotes cell proliferation; furthermore, the degradation of this matrix by the tumor is precisely what enables it to invade the surrounding tissue.

Additionally, tumor stroma forms around and within the tumor itself, composed of cancer-associated fibroblasts, tumor-associated macrophages, and blood vessels; in many tumors, this stroma accounts for the majority of the total tumor volume—even more than the tumor cells themselves.

When this tumor stroma becomes highly dense—as typically occurs in pancreatic cancer—it can prevent drugs from penetrating the tumor. This is a problem unrelated to the biology of the tumor cells themselves, but rather to the mechanical properties of the host tissue and the extracellular matrix that the tumor helped construct around itself.

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