ABSTRACT
Vacuolar ATPase (V-ATPase), specifically the a2 isoform, which is
discussed in this chapter, has been shown to be important in
tumor progression and metastases. V-ATPase is found as a multi-
protein complex found on the surface of tumors (Martinez-Zaguilan
et al. 1993, Sennoune et al. 2004b). Its role in tumorigenesis involves acidification of the extracellular environment via its proton
pumping activity. This activity enables maturation of pH-sensitive
degradative enzymes, such as matrix metalloproteinases, which
lead to tumor metastasis (Kubota & Seyama 2000, Rofstad et al. 2006). Increased cell surface expression of V-ATPases is linked to
cell invasion (Sennoune et al. 2004a). V-ATPase has at least three independent activities that support cancer growth by controlling
related inflammatory processes. The first is its function in the
control of hydrogen ion production. There ismounting evidence that
it also functions as a surface ATPase released from damaged and
necrotic cells (Derks & Beaman 2004a). It may be that the a2 isoform
has the capacity to redirect its activity and to be either an ATPase
or control acid hydrolysis on the cell surface. The second activity
is that of as a modulator of chemokines and cytokine expression
through a released peptide a2NTD (Jaiswal et al. 2012, Kwong et al. 2011). Finally, and perhaps most importantly, is its expression in
tumor macrophage where it can regulate IL-1 directly leading to
inflammation and subsequent angiogenesis.
