Sympathectomy decreases size and invasiveness of tongue cancer in rats

Abstract

The sympathetic nervous system plays a role in carcinogenesis wherein locally released sympathetic neurotransmitters affect proliferation, angiogenesis, vessel permeability, lymphocyte traffic and cytokine production. The present in vivo study was designed to investigate whether surgical sympathectomy, both unilateral and bilateral, had an effect on tumor growth, interstitial fluid pressure (IFP) and lymphatics in rat tongue cancer. We used 4-nitroquinoline-1-oxide (4-NQO) in drinking water for 19 weeks to induce tongue cancer in 20 Dark Agouti rats. After 11 weeks, one group underwent unilateral sympathectomy and another underwent bilateral sympathectomy, while the third group underwent sham surgery. By 19 weeks, tumors in the bilaterally sympathectomized (BL-SCGx) rats were significantly smaller (P<0.05), more diffuse in appearance and less invasive (P<0.05) compared with the large exophytic tumors in the sham-operated rats. The relative lymphatic area was significantly decreased (P<0.05) in tumors in the BL-SCGx rats compared with the sham group. Interestingly, the tumors in rats that underwent unilateral or bilateral sympathectomy had a significantly lower (P<0.05) IFP than those in sham rats. Lack of tyrosine hydroxylase (TH) immunoreactive nerves and few neuropeptide Y (NPY) positive fibers indicate absence of sympathetic nerve fibers in the bilateral sympathectomized group. The peritumoral lymph vessel area was correlated with the tumor size (P<0.001), depth of invasion (P<0.001), weight of rats (P<0.005) and IFP (P<0.05). In conclusion, the present study presents evidence that deprivation of sympathetic nerves decreases tumor growth in rat tongue, probably caused by decreasing IFP and lymph vessel area.