Specific N-Linked Glycosylation Patterns in Areas of Necrosis in Tumor Tissues.

ABSTRACT

Tissue necrosis is a form of cell death common in advanced and aggressive solid tumors, and is associated with areas of intratumoral chronic ischemia. The histopathology of necrotic regions appear as a scaffold of cellular membrane remnants, reflective of the hypoxia and cell degradation events associated with this cellular death pathway. Changes in the glycosylation of cell surface proteins is another common feature of cancer progression. Using a recently developed mass spectrometry imaging approach to evaluate N-linked glycan distributions in human formalin-fixed clinical cancer tissues, differences in the glycan structures of regions of tumor, stroma and necrosis were evaluated. While the structural glycan classes detected in the tumor and stromal regions are typically classified as high mannose or branched glycans, the glycans found in necrotic regions displayed limited branching, contained sialic acid modifications and lack fucose modifications. While this phenomenon was initially classified in breast cancer tissues, it has been also seen in cervical, thyroid and liver cancer samples. These changes in glycosylation within the necrotic regions could provide further mechanistic insight to necrotic changes in cancer tissue and provide new research directions for identifying prognostic markers of necrosis.