**3.1. Normal tissues**

These channel proteins exhibit a wide tissue distribution. Several AQPs (1–4) play a role in kidney function [36, 37]. For example, AQP 2 translocates from the intracellular vesicles to the apical plasma membrane of the collecting duct in response to vasopressin stimulation leading to water reabsorption by the kidney [37, 38]. AQP 1 allows carbon dioxide transport in the proximal tubules, for regulation of arterial pH during metabolic acidosis [39]. In the brain, AQP 4 is expressed in the perivascular astrocyte foot process region and plays a role in solute clearance from the interstitial fluid [40] and the neuro-excitatory processes [41]. In the skin, AQP 3 is expressed in the stratum corneum (SC) and plays a role in maintaining skin hydration and elasticity, and epidermal proliferation [42]. In the adipocytes, AQP 7 is involved in glycerol movement across the cell [36]. Several AQPs are expressed in various regions of the eye and play a role in ocular surface hydration, intraocular pressure regulation and visual signal transduction [43]. Other AQPs are expressed elsewhere but their physiological functions remain to be determined. For example, AQP 4 is expressed in the basolateral region of gastric parietal cells but its deletion in mice does not alter acid secretion [36, 44]. Furthermore, tissuespecific expression of AQP 4 in skeletal muscle [45], AQP 5 in sweat glands [46] and AQP 8 in various tissues [47] have not yet been linked with any specific physiological role.

### **3.2. Tumors**

There is accumulating evidence to suggest a role for several AQPs in cancer pathogenesis through their modulated expression profile in several tumors. It is speculated that AQPs facilitate water penetration into the growing tumor leading to its expansion through edema formation [48, 49]. They also appear to be involved in angiogenesis, tumor proliferation and migration/invasion [50–53]. About twenty types of tumors have been shown to express AQPs *in vivo*. For example, the expression level of AQPs 1, 4 and 9 are increased in astrocytoma [48, 54–57], while the level of AQP 1 was shown to be either increased [58] or decreased [59] in cholangiocarcinoma. Increased levels of AQPs 1, 3 and 5 [60–62] and decreased level of AQP 8 [63, 64] have been reported in colorectal cancer. In lung cancer, AQPs 1, 3, 4 and 5 were shown to be overexpressed [65–67]. Increased levels of AQPs 1, 3 and 5 were observed in cervical cancer [68, 69]. AQP 5 was increased in chronic myelogenous leukemia [70] and esophageal cancer [71]. In liver cancer, high levels of AQPs 3 and 5 [72] and low levels of AQPs 8 and 9 were observed [73].

There is a direct correlation between the expression level of several AQPs and tumor grade. High levels of AQPs 1, 4 and 9 were observed in astrocytoma correlating with advanced disease stage [48, 54–57]. Enhanced AQP 9 expression was evident in malignant compared to benign ovarian tissues and was positively correlated with tumor grade [74]. Furthermore, enhanced expression of AQP 1 was seen in lung adenocarcinoma and its inhibition reduced cell invasion [66].
