Can heparins stimulate bone cancer stem cells and interfere with tumorigenesis?

Heparin and heparan sulfate, a variety of negatively charged highly sulfated polysaccharides, can influence the biological functions of human bone morphogenetic proteins (BMPs). Notably, BMPs control numerous essential biological activities and processes, such as bone formation, bone turnover, brain development, tumor initiation, and progression. BMPs also enhance the repair of bone tissue injuries and are used in bone remodeling alongside implantable prosthetic devices. BMPs either potentiate or inhibit the growth of cancer stem cells (CSCs). This dual biological effect appears to depend upon the cell type, underlying cytogenetic and biochemical aberrations in various distinct malignancies. Similarly, heparins may modulate CSCs positively or negatively through BMPs. The primary aims of this review are to investigate whether heparin prophylaxis would likely stimulate the propagation of a chemotherapy-resistant subpopulation of CSCs and aggravate tumor response to treatment, and result in tumor expansion, tumor recurrence and metastasis. The secondary aim is to document whether such detrimental effects surpass their beneficial effects as anticoagulants in primary bone cancers such as osteosarcoma. The current state of scientific knowledge based on key published articles from the standpoint of rigidity of data and identification of data gaps is discussed.