Hyaluronic acid (HA) is a prominent component of the extracellular matrix, and its interactions with HA-interacting molecules (HAIMs) play a critical role in cancer development and disease progression. This review explores the multifaceted role of HAIMs in the context of cancer, focusing on their influence on disease progression by dissecting relevant cellular and molecular mechanisms in tumour cells and the tumour microenvironment. Cancer progression can be profoundly affected by the interactions between HA and HAIMs. They modulate critical processes such as cell adhesion, migration, invasion, and proliferation. The TME serves as a dynamic platform in which HAIMs contribute to the formation of a unique niche. The resulting changes in HA composition profoundly influence the biophysical properties of the TME. These modifications in the TME, in conjunction with HAIMs, impact angiogenesis, immune cell recruitment, and immune evasion. Therefore, understanding the intricate interplay between HAIMs and HA within the cancer context is essential for developing novel therapeutic strategies. Targeting these interactions offers promising avenues for cancer treatment, as they hold the potential to disrupt critical aspects of disease progression and the TME. Further research in this field is imperative for advancing our knowledge and the treatment of cancer.

Capillary morphogenesis gene 2 (CMG2) mediates cell–matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell–cell, cell–matrix and cell–hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation.