Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells

Abstract

One of the main problems of modern health care is the growing number of oncological diseases both in the elderly and young population. Inadequately effective chemotherapy, which remains the main method of cancer control, is largely associated with the emergence of multidrug resistance in tumor cells. The search for new solutions to overcome the resistance of malignant cells to pharmacological agents is being actively pursued. Another serious problem is immunosuppression caused both by the tumor cells themselves and by antitumor drugs. Of great interest in this context is heparin, a biomolecule belonging to the class of glycosaminoglycans and possessing a broad spectrum of biological activity, including immunomodulatory and antitumor properties. In the context of the rapid development of the new field of “osteoimmunology,” which focuses on the collaboration of bone and immune cells, heparin and delivery systems based on it may be of intriguing importance for the oncotherapy of malignant bone tumors. Osteosarcoma is a rare but highly aggressive, chemoresistant malignant tumor that affects young adults and is characterized by constant recurrence and metastasis. This review describes the direct and immune-mediated regulatory effects of heparin and drug delivery systems based on it on the molecular mechanisms of (multiple) drug resistance in (onco) pathological conditions of bone tissue, especially osteosarcoma.

Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis

“…CD271 is known to be a receptor for neural crest growth factor and is the marker for bone marrow-derived MSCs [391]. OS-CSCs are characterized by drug resistance associated with high DNA repair capacity, inhibition of apoptotic signaling, increased lysosomal activity due to overexpression of vacuolar ATP, and enhanced drug efflux due to overexpression of ABC transporters [10,32,392].…”

“…However, chemotherapeutic approaches to the treatment of OS are effective only for localized OS. Progressive, metastatic, and recurrent OS are associated with the development of chemoresistance and poor prognosis [10]. More than 30% of patients with localized OS and more than 80% of patients with metastatic/recurrent disease die from the formation of resistant tumor subclones [11].…”

“…Nevertheless, the search for specific molecular targets and promising innovative approaches in OS therapy, including drug delivery methods, is an urgent problem [10]. Modern regenerative medicine focuses on harnessing the potential of mesenchymal stem cells (MSCs) because they have low immunogenicity [13].…”

Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues

“…The search for ways to overcome these pharmacologically resistant malignant cells is thus an important clinical objective. Heparin has broad biological activity, including roles in immunomodulation, and could potentially be focused to alleviate these antitumor effects [ 203 ]. Osteosarcoma is an example of a rare, highly aggressive, chemoresistant malignant tumor affecting young adults and characterized by recurrence and metastasis.…”

“…Osteosarcoma is an example of a rare, highly aggressive, chemoresistant malignant tumor affecting young adults and characterized by recurrence and metastasis. The direct and immune-mediated regulatory effects of heparin on drug delivery systems in pathological bone tissue such as osteosarcoma is producing significant improvement in the treatment of these clinically difficult tissues [ 203 ]. Bone tumors are difficult to treat, with the efficacy of the therapeutic agents being compromised by the physiological bone environment.…”