Perineural lymphatics: Myth or fact

Larson, Duane L.; Rodin, Alvin E.; Roberts, Daniel K.; O'Steen, W. Keith; Rapperport, Alan; Lewis, S. R.

doi:10.1016/0002-9610(66)90309-6

Cited by 142 publications

(58 citation statements)

References 7 publications

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“…Better understanding of PNI pathogenesis could bring about effective control of PNI-related morbidities, such as local recurrence and extrapancreatic spread. Initially, PNI was believed to be the lymphatic spread of tumors into nerves (9); however, later studies confirmed there were no lymphatic vessels in the nerve (8). The next predominant theory was that the nerve sheath served as a low-resistance path for tumor spread.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, the hypotheses of PNI research were mainly focused on anatomy, including the lymphatic spread of tumors into nerves (8,9) and the nerve sheath as a low-resistance path for tumor spread (10). More recently, on the basis of the neurotropism theory, in which tumor cells invade nerves mediated by neurotrophins, a new hypothesis of PNI was raised that emphasized the reciprocal signaling interactions between the nerves and invading tumor cells (7).…”

Section: Introductionmentioning

confidence: 99%

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Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Guo

et al. 2013

Molecular Cancer Therapeutics

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Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells cocultured in vitro, cellular and molecular biology, and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking b-adrenergic receptors (AR) and by blocking protein kinase A, but not through blocking a-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2, and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the b-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Guo

et al. 2013

Molecular Cancer Therapeutics

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“…However, there is no anatomical description of the space between the perineurium and the nerve bundle, even though perineural invasion has been identified in carcinoma. This space attracts attention as the perineural space 24,25) . From the results of experimental and clinical studies, it has become generally accepted that the perineural space does not communicate with the lymphatic system 24,25) .…”

Section: Discussionmentioning

confidence: 99%

“…This space attracts attention as the perineural space 24,25) . From the results of experimental and clinical studies, it has become generally accepted that the perineural space does not communicate with the lymphatic system 24,25) . Although, it is evident that the perineural space exists between the perineurium and nerve bundle of autonomic nerves, research regarding the existence of the perineural space in somatic nerves has not been performed.…”

Section: Discussionmentioning

confidence: 99%

Histopathological Changes in Surrounding Tissue of the Sciatic Nerve after Spinal Cord Injury in Rats

et al. 2012

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Abstract.[Purpose] The purpose of this study was to examine histopathological changes in tissue surrounding the sciatic nerve after spinal cord injury (SCI) in rats. [Subjects and Methods] Thirty adult, nine-week-old, female Wistar rats were used in this study. Fifteen experimental rats underwent spinal cord transection at the level of Th8-9 and the other fifteen control rats were raised normally. Animals were assessed at 1, 2, 4, 8, and 12 weeks following surgery. After the experimental period, we obtained tissue surrounding the sciatic nerve of the thigh after hematoxylin and eosin staining under a microscope. [Results] Adherence between the nerve bundle and perineural innermost layer was observed in tissue surrounding the sciatic nerve in the SCI group. Adherence among the interperineurium was evident at 2 weeks after SCI. It had declined at 4 weeks after SCI, but was still evident at 8 and 12 weeks after SCI. [Conclusion] Histopathological findings in the SCI model may be related to compression of the nerve bundle and neurogenic contracture of tissue surrounding the nerve bundle.

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“…The perineural spaces of the nerves were often called perineural lymphatics because they were considered to be continuous with and leading to the lymphatic system in the connective tissues surrounding the nerve. Larson et al (1966), however, gave experimental findings inconsistent with this assumption. India ink injected into the lymphatics of animals was demonstrated not to reach the perineural spaces (Rodin et al 1967).…”

Section: Discussionmentioning

confidence: 99%

Perineural Tumor Invasion and Its Relation with the Lymphogenous Spread in Human and Experimental Carcinoma of Bile Duct. A Computer-aided 3-D Reconstruction Study.

Suzuki

Takahashi

Ouchi

et al. 1994

Tohoku J. Exp. Med.

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Perineural lymphatics: Myth or fact

Cited by 142 publications

References 7 publications

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Histopathological Changes in Surrounding Tissue of the Sciatic Nerve after Spinal Cord Injury in Rats

Perineural Tumor Invasion and Its Relation with the Lymphogenous Spread in Human and Experimental Carcinoma of Bile Duct. A Computer-aided 3-D Reconstruction Study.

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