The Study On Endogenous Electric Field And Ion Flux In Microenvironment Of Mouse Skin Melanoma

Background As an important signal, electric field may guide cell migration promote cell proliferation and induce cell orientation. Ion channels on the plasma membrane of tumor cells transport different ions into/out of the cytoplasm which results in the membrane potential alone the plasma membrane. The asymmetric distribution of the ion channels alone different tissue is the fundamental of the endogenous electric field.Many researches showed that the endogenous electric field is one of the important factors in tumor microenvironment which may play a role in the tumor growth and metastasis. Thus the scanning vibrating electrode technique（SVET） and the selected ionic electrode technique（SIET） were applied to study the endogenous electric field and ionic flux in tumor microenvironments during tumor growth and metastasis with the mice skin melanoma as model. Moreover, the electric field directed melanoma cell migration were studied as well.The results indicated that:1)The endogenous electric field is abnormal at tumor site comparing with that of the normal skin.At the 6th day of the inoculation, the electric current is-5.57±1.10μA/cm2（ n=3） at tumor edge. At the 9th day of inoculation, the current value is-7.17±1.85 μA/cm2（n=3）at tumor edge. All the electric current is toward the opposite direction comparing to that of the normal skin2)The Potassium, Sodium and Chloride flux is abnormal at the tumor site comparing with that of the normal skin.a) At vertical direction of the tumor tissue, the sodium ions flux is-3700.39±889.63 pmol/cm^-2/sec（n=3）, the chloride ions flux is-9305.68±1449.91pmol/cm^-2/sec（n=4）, the potassium ions flux is 274.86±55.32 pmol/cm^-2/sec（n=3）. It has a significant difference with normal skin tissue. While the calcium ion flow is-13.12±6.67pmol/cm^-2/sec（n=4）, there was no significant difference with normal skin tissue.b) At the horizontal direction of the tumor tissue, the sodium ions flux is-1913.51±500.64 pmol/cm^-2/sec（n=4）, the chloride ions flux is-11004.39±2643.16 pmol/cm^-2/sec（n=3）, the potassium ions flux is321.17±98.78pmol/cm^-2/sec（n=3）, It has a significant difference with normal skin tissue. And the calcium ion flow is-20.05±6.73pmol/cm^-2/sec（n=3）. There was no significant difference with normal skin tissue.3)The physiological electric field can guide melanoma cell migration toward anode.a) The directedness increased with voltage gradually which exhibited voltage dependence（-0.307±0.055 to-0.616±0.045, n≥140）.b) The track speed, Displacement speed and Persistency increase with the voltage strength in the 100⁴00m V/mm.Then all of those three parameters decreased at the 500 m V/mm voltage.Conclusion: The endogenous electric field in tumor microenvironments is abnormal during tumor growth. The sodium flux, chloride flux and potassium flux are the major ions contribute to the abnormal of the endogenous electric fields. In vivo experiments showed that the physiological strength of the small directed electric field can guided melanoma cell migration toward anode. The migration speed, directness and persistence would increase with the strength of voltage at the range of 100⁴00m V/mm.