Why are olfactory ensheathing cell tumors so rare?

Abstract

The glial cells of the primary olfactory nervous system, olfactory ensheathing cells (OECs), are unusual in that they rarely form tumors. Only 11 cases, all of which were benign, have been reported to date. In fact, the existence of OEC tumors has been debated as the tumors closely resemble schwannomas (Schwann cell tumors), and there is no definite method for distinguishing the two tumor types. OEC transplantation is a promising therapeutic approach for nervous system injuries, and the fact that OECs are not prone to tumorigenesis is therefore vital. However, why OECs are so resistant to neoplastic transformation remains unknown. The primary olfactory nervous system is a highly dynamic region which continuously undergoes regeneration and neurogenesis throughout life. OECs have key roles in this process, providing structural and neurotrophic support as well as phagocytosing the axonal debris resulting from turnover of neurons. The olfactory mucosa and underlying tissue is also frequently exposed to infectious agents, and OECs have key innate immune roles preventing microbes from invading the central nervous system. It is possible that the unique biological functions of OECs, as well as the dynamic nature of the primary olfactory nervous system, relate to the low incidence of OEC tumors. Here, we summarize the known case reports of OEC tumors, discuss the difficulties of correctly diagnosing them, and examine the possible reasons for their rare incidence. Understanding why OECs rarely form tumors may open avenues for new strategies to combat tumorigenesis in other regions of the nervous system.

Key differences between olfactory ensheathing cells and Schwann cells regarding phagocytosis of necrotic cells: implications for transplantation therapies

“…As the turnover of neurons is a normal and continuous process, it is important that an inflammatory environment is not created by the OECs that would otherwise comprise the functioning of the olfactory nerve. Similarly, recruitment of macrophages is not desirable as it would require continual infiltration of macrophages into the olfactory nerve 13,60 . Indeed, rather than attracting macrophages, OECs appear to repel these cells; MIF secretion from both OECs and macrophages have been shown important for this segregation 12 .…”

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

“…The SCs secrete inflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and IL-1α (Fregnan et al, 2012) which results in recruitment of macrophages to the site of injury. As hematogenous macrophages enter the injury site later, it is estimated that the initial 40-50% of the debris clearance is performed by SCs along with help from the resident endoneurial macrophages (Perry et al, 1995;Mueller et al, 2003). The exact time of arrival of hematogenous macrophages is unknown.…”

“…The exact time of arrival of hematogenous macrophages is unknown. Previous work in rodents reports macrophage arrival at the lesion site almost 2-3 days after injury, with numbers peaking between day 7 and 14 (Perry et al, 1987;Stoll et al, 1989;Taskinen and Roytta, 1997;Bendszus and Stoll, 2003;Mueller et al, 2003). One study reported the presence of infiltrating macrophages as early as 36 h after mouse sciatic nerve axotomy (Beirowski et al, 2004).…”

“…The perineurium in turn envelops the endoneurium consisting of Schwann cell-axonal structures, fibroblasts and resident macrophages (Shanthaveerappa and Bourne, 1963;Bonetti et al, 1993;Reina et al, 2015;Wolbert et al, 2020). After the breakdown of the BNB in the case of an injury or infection, peripheral immune cells (particularly macrophages) are recruited to the peripheral nerves (Perry et al, 1987;Taskinen and Roytta, 1997;Tofaris et al, 2002;Mueller et al, 2003;Beirowski et al, 2004). The peripheral nerve resident macrophages known as endoneurial macrophages, along with the glial cells contribute to the initial phagocytic clearance and aid in nerve-regeneration following injury (Mueller et al, 2003;Wang et al, 2020).…”

“…After the breakdown of the BNB in the case of an injury or infection, peripheral immune cells (particularly macrophages) are recruited to the peripheral nerves (Perry et al, 1987;Taskinen and Roytta, 1997;Tofaris et al, 2002;Mueller et al, 2003;Beirowski et al, 2004). The peripheral nerve resident macrophages known as endoneurial macrophages, along with the glial cells contribute to the initial phagocytic clearance and aid in nerve-regeneration following injury (Mueller et al, 2003;Wang et al, 2020). However, in the unperturbed PNS, the resident glia are the main phagocytes (Bishop et al, 2004;Wu et al, 2009;Su et al, 2013;Nazareth et al, 2015a).…”