Schwann cells induce cancer cell dispersion and invasion

Deborde, Sylvie; Omelchenko, Tatiana; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William; Chernichenko, Natalya; Lee, Sei Young; Barajas, Fernando; Chen, Chun‐Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

doi:10.1172/jci82658

Cited by 178 publications

(276 citation statements)

References 67 publications

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“…Although the role of neural cell adhesion molecules has been widely described to contribute to cancer pathogenesis17, 18, 19, 20, 21, 22, 23 and nonparaneoplastic autoimmune neuropathies,10, 24, 25 the results in our study suggest that nerve damage in our cohort cannot be attributed to a humoral autoimmune attack targeting L1CAM and NCAM1 or the nodal/paranodal CNTN1/CASPR1 complex, CNTN1, NF140, NF155, or NF186. However, this lack of antibodies should be confirmed in further studies involving other cohorts of PN.…”

Section: Discussioncontrasting

confidence: 53%

“…Two of our CIDP patients harboring antibodies against CNTN1, respectively, developed a lymphoma and a colon adenocarcinoma in addition to their neuropathy, one of them concomitantly, and the other several years later. The role of other cell adhesion molecules such as neural cell adhesion molecule 1 (NCAM1)17, 18, 19, 20 and L1 (L1CAM)21, 22, 23 in cancer pathogenesis has been widely described. However, their possible involvement as antigens in paraneoplastic neuropathies has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Siles

Martínez‐Hernández

Araque

et al. 2018

Ann Clin Transl Neurol

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ObjectiveParaneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN).MethodsThirty‐four patients fulfilling diagnostic criteria of possible (n = 9; 26.5%) and definite (n = 25; 73.5%) PN without onconeural antibodies and 28 healthy controls were included in our study. Sera were tested for known antibodies against neural cell adhesion molecules and screened for novel IgG and IgM reactivities against nerve components: dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells. Patients showing autoantibodies against any of these cell types were used for immunoprecipitation (IP) studies.ResultsOverall, 9 (26.5%) patients showed significant reactivity against DRG neurons, motor neurons, or Schwann cells, whereas 5 (17.9%) healthy controls only showed moderate reactivity. Compared with control sera, serum samples from patients with paraneoplastic sensory‐motor neuropathies had a higher frequency of IgM antibodies against Schwann cells (0% vs. 40%; P = 0.0028). No novel antigens were identified from our IP experiments. Antibodies against the neural adhesion molecules CNTN1, NF155, NF140, NF186, NCAM1, L1CAM, and the CNTN1/CASPR1 complex were not detected in patients with PN. One (2.9%) patient with CIDP and thymoma had CASPR2 antibodies.InterpretationAlmost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm‐associated antigens remain to be discovered.

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Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Siles

Martínez‐Hernández

Araque

et al. 2018

Ann Clin Transl Neurol

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“…Patients who experience perineural invasion, which has been described in many cancer types, often have poor prognoses, higher risk of local recurrence, and often suffer from severe pain (10,11). In this issue, Deborde et al uncover a key mechanism of perineural invasion that is mediated by direct contact between Schwann cells and cancer cells (12).…”

Section: The Nerve Microenvironment and Cancer Progressionmentioning

confidence: 99%

“…A bundle of Schwann cells can also invaginate between individual axons to isolate them from one another (14). In this issue, Deborde et al demonstrate that cancer exploits some of these canonical functions of Schwann cells in neuronal repair and regulation to promote cancer cell perineural invasion (12). Their findings suggest that the dedifferentiated subtype of Schwann cells associated with nerve repair is activated in cancer, as they observed a substantial increase of the dedifferentiated Schwann cell marker GFAP in tumor nerves compared with that in normal nerves in both clinical samples and a murine model of perineural invasion.…”

Section: Schwann Cell-mediated Perineural Invasion Requires Contactmentioning

confidence: 99%

“…In particular, only dedifferentiated Schwann cells closely associated with cancer cells, while differentiated Schwann cells did not. While Schwann cells have previously been implicated in perineural invasion based on examination of histological sections (19), Deborde et al functionally demonstrate a cellular and molecular mechanism for Schwann cell involvement in perineural invasion (12).…”

Section: Schwann Cell-mediated Perineural Invasion Requires Contactmentioning

confidence: 99%

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Cancer’s got nerve: Schwann cells drive perineural invasion

Azam¹,

Pecot²

2016

Journal of Clinical Investigation

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C o m m e n t a r y The nerve microenvironment and cancer progressionWhile the involvement of blood and lymphatic vessels in tumor growth and progression is well established, the role of nerves in the tumor microenvironment has been largely underappreciated. Increasing evidence suggests that activation of nerve growth into tumors, termed neoneurogenesis, is another key driver of cancer progression. In addition, chronic activation of the sympathetic nervous system via increased norepinephrine levels has been observed in the tumor microenvironment (1, 2), and this activation has been demonstrated to promote tumor growth and progression via β-adrenergic receptor signaling on tumor cells and subsequent upregulation of tumor-promoting chemokines (3-6). However, it was the hallmark paper from Magnon et al. (7) that clearly demonstrated that neuronal involvement promotes cancer progression. Specifically, this group showed that autonomic nerve formation is important for regulating primary prostate cancer growth and metastasis in mouse models and that inhibition of stromal β-adrenergic receptor and type 1 muscarinic receptor signaling inhibits tumor development and improves survival. Similarly, Zhao et al. (8) recently demonstrated that stomach denervation in mouse models of gastric cancer reduces tumor incidence and growth while improving chemotherapy response and that muscarinic acetylcholine M3 receptor loss inhibits tumorigenesis. Together, these groundbreaking studies also revealed that high tumor neural fiber density strongly correlates with tumor stage and worse clinical outcome, further implicating neuronal involvement as a key driver in cancer. Perineural invasion is the growth and invasion of cancer cells around and into nerves present in the tumor microenvironment (9). This is believed to promote tumor progression by providing a conduit for cancer cell spread. Patients who experience perineural invasion, which has been described in many cancer types, often have poor prognoses, higher risk of local recurrence, and often suffer from severe pain (10, 11). In this issue, Deborde et al. uncover a key mechanism of perineural invasion that is mediated by direct contact between Schwann cells and cancer cells (12). Schwann cell-mediated perineural invasion requires contactSchwann cells regulate neuronal growth, survival, and repair (13, 14) and undergo dedifferentiation into a more migratory subtype to promote neuronal guidance through matrix remodeling, paracrine signaling, and induction of neuron axonal extensions via direct cellular contact (15-18). A bundle of Schwann cells can also invaginate between individual axons to isolate them from one another (14). In this issue, Deborde et al. demonstrate that cancer exploits some of these canonical functions of Schwann cells in neuronal repair and regulation to promote cancer cell perineural invasion (12). Their findings suggest that the dedifferentiated subtype of Schwann cells associated with nerve repair is activated in cancer, as they observed a substantial increase ...

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Emerging life sciences series: Q&A with the Editor

Montano¹

2022

Advanced Biology

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perineural invasion on patients' quality of life, which led to my decision to deepen my understanding of the crosstalk between cancer and the nervous system. At that time, I was not yet aware of the complexity of these interactions, so I was fortunate that my advisor, Dr. Gil, was interested in the dialogue among cancer cells, the immune system, and the nervous system. This led me to learn how to study complex systems using in vivo and in vitro models to recapitulate the neural niche of the tumor microenvironment and the multiple cell types involved in these interactions.2. Can you tell us about some key scientific developments that led to your current thinking about the tumor microenvironment, immune response and health outcomes?

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Schwann cells induce cancer cell dispersion and invasion

Cited by 178 publications

References 67 publications

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Cancer’s got nerve: Schwann cells drive perineural invasion

Emerging life sciences series: Q&A with the Editor

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