Na-K-2Cl cotransporter and aquaporin 1 in arachnoid granulations, meningiomas, and meningiomas invading dura

SummaryMeningioma invasion of the dura may contribute to the high rate of recurrence. Recently, ion channels that affect cell shape and movement have been implicated in cancer invasion. Combined Na-K-2Cl cotransporter (NKCC1) and aquaporin 1 (AQP1) expression in arachnoid granulations and meningiomas with and without dural invasion has not been characterized. Arachnoid granulations associated with dura were collected from 10 adult formalin-fixed dura/leptomeninges. Thirty-four frozen meningiomas were evaluated by Western blot. An additional 58 formalin-fixed, paraffin-embedded meningiomas including 36 World Health Organization grade I, 15 grade II, and 7 grade III meningiomas were evaluated by immunohistochemistry. By Western blot, NKCC1 was found in 17 (100%) of 17 World Health Organization grade I, 13 (87%) of 15 grade II, and both grade III meningiomas. Distinct AQP1 was not detected in the meningioma lysates tested. By immunohistochemistry, extensive NKCC1 but no AQP1 immunoreactivity was detected in the arachnoid granulation cells. Extensive NKCC1 was detected in meningioma cells in 56 and in capillaries in 43 by immunohistochemistry. In those tumors with dural or bone/soft tissue invasion, NKCC1 immunoreactivity was seen in invading cells in all cases and in their capillaries in the majority. AQP1 was detected in meningioma cells in 29 and in capillaries in all. AQP1 was also detected in cells and capillaries invading the dura or bone in 10 and 18 of 18, respectively. This was extensive in all subtypes of meningiomas studied. These findings suggest that NKCC1 and AQP1 participate in meningioma biology and invasion. NKCC1 might be targeted by FDA-approved NKCC1 inhibitors.