The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

Paraneoplastic immune-mediated disorders have been well described in the literature. However, it is still relatively rare. The incidence has increased over the past decade due largely to the discovery of more autoantibodies. With a better understanding of the pathophysiology of different autoantibodies and clinical phenotypes, we are often able to diagnose clinically some specific paraneoplastic autoimmune neurological syndromes. We may also predict the response to treatment based on the autoantibody class. We are presenting a very unusual case of two completely different paraneoplastic syndromes with two different autoantibodies, gamma-aminobutyric acid-B (GABAB) and collapsin response mediator protein 5 (CRMP5), in a patient with underlying small-cell lung cancer. We will discuss the differences in the two antibody syndromes, their significance, and their management.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Collapsin response mediator protein 5 (CRMP5) belongs to a family of five cytosolic proteins that serve a major role in neural development. CRMP5 has been identified as a biomarker of numerous cancer types, including lung cancer and glioblastoma. However, the role of CRMP5 in CRC remains unclear. In the present study, CRMP5 was characterized as a novel biomarker of poor survival in CRC. CRMP5-overexpression in CRC cells promoted cell proliferation and migration while CPMP5-knockdown decreased cell growth and migration. A novel mechanism was uncovered, by which CRMP5 regulates MAPK signaling to drive CRC cell proliferation and development. Furthermore, CRMP5-overexpression induced chemotherapy resistance and tumor recurrence in CRC. Taken together, these results demonstrated the important role of CRMP5 in the development and proliferation of CRC cells and suggested that CRMP5 may be a novel therapeutic target for CRC.

Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

Collapsin response mediator protein 5 (CRMP5), a member of the CRMP family, is expressed in the brain, particularly in the hippocampus, an area of the brain that can modulate stress responses. Social stress has a well-known detrimental effect on health and can lead to depression, but not all individuals are equally sensitive to stress. To date, researchers have not conclusively determined how social stress increases the susceptibility of the brain to depression. Here, we used the chronic social defeat stress (CSDS) model and observed higher hippocampal CRMP5 expression in stress-susceptible (SS) mice than in control and stress-resilient (RES) mice. A negative correlation was observed between the expression levels of CRMP5 and the social interaction (SI) ratio. Reduced hippocampal CRMP5 expression increased the SI ratio in SS mice, whereas CRMP5 overexpression was sufficient to induce social avoidance behaviors in control mice following exposure to subthreshold social stress induced by lentivirus-based overexpression and inducible tetracycline-on strategies to upregulate CRMP5. Interestingly, increased CRMP5 expression in SS and lenti-CRMP5-treated mice also caused serum corticosterone concentrations to increase. These findings improve our understanding of the potential mechanism by which CRMP5 triggers susceptibility to social stress, and they support the further development of therapeutic agents for the treatment of stress disorders in humans.

Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer associated with a broad spectrum of clinical manifestations. Optic neuropathy (ON) and myelitis are frequent manifestations of multiple sclerosis and neuromyelitis optic spectrum disorders but are considered as non-classical in PNS. Here, we report a case of PNS revealed by simultaneous bilateral ON and myelitis related to a cluster of three neural autoantibodies, in the setting of small cell lung cancer.

CV2/CRMP5 is the most common antibody accompaniment of paraneoplastic choreoathetosis. We present a case of paraneoplastic choreothetosis with associated cerebellar dysfunction, peripheral neuropathy, and likely dysautonomia. Our patient developed a movement disorder after a cardiopulmonary arrest, which unfortunately masked the true etiology of his symptoms. He was later found to have extensive stage small cell lung cancer, with further evaluation revealing seropositivity for anti-CV2 antibodies. Choreoathetosis is a known sequelae of hypoxic-ischemic brain injury, but clinicians should continue to keep an open mind. The utility of immunotherapy is unclear in these circumstances and many physicians adopt a symptom-based approach.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological condition with many associated risk factors. The presentation varies and consists of seizures, impaired visual acuity or visual field deficits, disorders of consciousness, headaches, confusion and focal neurological deficits. The diagnosis relies on clinical presentation and MRI findings. Treatment and prognosis are related to the underlying etiology.
METHODS: We present a 58-year-old woman with ovarian cancer who developed symptoms and radiologic signs of PRES with no apparent trigger other than a sudden increase in blood pressure for the first time in her life and before any treatment has begun. Antibodies to collapsin response-mediator protein-5 (CRMP-5), a malignancy related paraneoplastic protein, were identified in her CSF.
CONCLUSIONS: We present a novel and intriguing association between PRES and antibodies against CRMP-5 which may highlight a new etiology for this condition.

We herein report a 76-year-old man who developed irritability and forgetfulness 5 months after the introduction of atezolizumab for the treatment of small cell lung cancer (SCLC). Brain magnetic resonance imaging showed lesions of the striatum, and an investigation of the serum revealed a high titer of anti-CRMP5 antibody. After stopping atezolizumab and starting steroid pulse therapy, these clinical features improved. Given these findings, it is considered that CRMP5-assciated striatal encephalitis was induced by atezolizumab in this case with SCLC.