*1.1.5. Human breast telocytes*

Recently, several papers were describing the presence of a new cellular type—the telocytes (TCs)—in the stroma of the mammary gland [57–59]. TCs are characterized by a small cellular body and extremely long telopodes with alternative regions of dilations called podoms and veillike cytoplasmic extensions called podomeres [60–62]. Although there are numerous attempts to differentiate these cells from other cellular types such as fibroblasts, endothelial cells, mesenchymal stem cells, immune cells, a specific immunohistochemical marker was still not found [63]. The most specific markers, which are nowadays used for their identification, are CD34 and PDGFR alpha or beta [64, 65]. Genomic and proteomic approaches were also used to determine their uniqueness and have shown that telocytes are distinct from the other types listed above [66–70].

Mou et al. investigated the immunohistochemical characteristics and potential functions of TCs in reconstituted breast cancer tissue and found that they express c-kit/CD117, CD34, and vimentin. A very interesting observation is that TCs communicate with breast cancer cells as well as with other stromal cells [58, 71, 72]. Together with other stromal cells, TCs inhibited the breast cancer cell apoptosis and facilitated their proliferation and the formation of typical nest structure assembly in breast cancer, in vitro [58].

human mammary epithelial cells [76]. Additionally, breast cancer cells react distinctly with respect to normal mammary epithelial cells in response to the changes in the extracellular ions (e.g., K<sup>+</sup>

**Figure 2.** Proteins associated with calcium signaling pathways that have been described to undergo alterations in breast

Ca2+) [76]. The differences in resting potential between breast cancer cells and normal cells may be useful in the development of anticancer-targeted therapies based on charged liposomes, which

MDA-MB-231 breast cancer cells with high-metastatic potential also exhibit spontaneous Ca2+ oscillations in comparison with MCF7 breast cancer cells with a low-metastatic potential [78]. Interestingly, these spontaneous oscillations were absent in breast cancer cells with

determined the augmentation of their basal Ca2+ level [78]. This feature of presenting spontaneous calcium oscillations in metastatic cells might be further exploited in understanding the

Patch-clamp studies on human mammary epithelial cells (HMEC) indicated the absence of

The contribution of T-type calcium channels to breast cancer was investigated in several studies. To date, the expression of the α1H subunit, but not the α1C or α1G subunits, of the voltage-gated calcium channels was demonstrated in MCF-7 breast cancer cells [80]. Among T-type calcium channels, Cav3.1, but not Cav3.2, was demonstrated to play an important

are considered among the promising liposome-based therapeutical approaches [77].

a low-metastatic potential, even in increased extracellular K<sup>+</sup>

**2.2. Voltage-gated calcium channels in breast cancer**

voltage-gated calcium currents [79].

cancer cells.

cellular mechanisms standing behind and in finding adequate therapies.

or

173

concentration conditions that

Alterations in Calcium Signaling Pathways in Breast Cancer

http://dx.doi.org/10.5772/intechopen.80811

Rusu et al. described in an immunohistochemical study some CD34+/CD10±/c-kit-/vimentincells found in the inter- and intralobular stroma, which they considered to be TCs and suggested a stem cell-like features based on the expressed markers and changing phenotype [59]. Although a lot of studies are needed to talk about a certain function of TCs, a possible contribution to the mechanisms of carcinogenesis is not negligible, by the modification of the tumor microenvironment. As our team previously showed, TCs are not pacemakers but modulate the activity of the surrounding cells using calcium signaling [73]. Our results showed that uterine TCs express T-type calcium channels that might play a role in the generation of endogenous bioelectric signals responsible for the regulation of the surrounding cell behavior [74, 75].
