**4.3. Lung cancer**

14 Dehydrogenases

breast cancer progression.

lines (Marcato*, et al.*, 2011).

authentic role of BCSCs' chemotherapy resistance.

Breast CSCs were initially isolated, established on cell surface marker with CD24/lowCD44 expression. More currently, ''functional'' markers depending on stem cell properties are investigated for their plausible applications in the breast CSCs isolation. By this method, applying the aldefluor assay (Stemcell Technologies), originally designed to isolate viable HSCs and is an enzyme-based assay that recognizes ALDH activity, Ginestier et al. isolated breast CSCs. The assay is thought to precisely recognize ALDH isoform ALDH1A1 activity degree. Besides its application as a prognostic and CSC marker, ALDH activity that is primarily carried out by ALDH1A3 might be functional in

Expression of genes and tumor sphere formation in self-renewal and differentiation could be changed by adding chemical RA signaling inducers or inhibitors in breast cancer cell

ALDH1 could work as a marker of breast CSCs better than CD44+/CD24-. Though we could not maintain a conclusion that ALDH1 expression was significantly related with any conventional clinicopathologic attributes, nevertheless, there is a compelling relation between ALDH1-positive breast tumors and resistance to neoadjuvant chemotherapy, because of the pCR rates being obtained, which are lower in ALDH1-positive tumors (9.5%) than ALDH1-negative tumors (32.2%). Moreover, after neoadjuvant chemotherapy, a considerable increase in the proportion of ALDH1-positive tumor cells was observed. These results are an indication of ALDH1-positive tumor cells playing an important role in resistance to chemotherapy. Because of tumor cells being more tumorigenic than CD44+/CD24-, tumor cells of breast CSCs are thought to be richer in ALDH1-positive tumor cells than in CD44+/CD24- tumor cells. As a matter of course, we have shown that ALDH1 positive, in contrast with CD44+/CD24-, is closely associated with colony formation in the collagen gel as well. The subset of ALDH1-positive and CD44+/CD24- tumor cells has been reported to contain the largest proportion of breast cancer stem cells (BCSCs); consequently, it is speculated to have the strongest resistantance to chemotherapy. However, in our current study, pCR rates in the ALDH1-positive and CD44+/CD24- high subset (20%, 2 of 10), are not the lowest among all the subsets consisting of the ALDH1-positive and CD44+/CD24- low subset (0%, 0 of 11), the ALDH1-negative and CD44+/CD24- high subset (34.1%, 15 of 44), and the ALDH1-negative and CD44+/CD24- low subset (30.2%, 13 of 43). Adding CD44/CD24 status to ALDH1 status does not seem to positively improve the prediction of response to chemotherapy. Together, these results direct us to assume that, at least for the prediction of resistance to chemotherapy, ALDH1-positive tumor cells serve as a better marker for BCSCs than CD44+/CD24- tumor cells. Because such tumors contain a higher proportion of CSCs, we suppose that ALDH1- positive tumors are resistant to chemotherapy. However, because ALDH1 has been shown to play an important role in the resistance to chemotherapy in hematopoietic cells, ALDH1-positive tumor cells might be involved in resistance to chemotherapy, regardless of whether they are CSCs or not. In addition to deeper illumination of ALDH1's function in chemotherapy resistance in breast cancers, obtaining a significantly specific marker for BCSCs is necessary to enlighten an Each year, approximately 171,000 new cases of lung cancer are diagnosed, and 160,000 individuals do not survive from the disease in the United States. This high incidence and mortality makes lung cancer one of the most common cancers and the leading cause of cancer death in men. Lung cancer is still the leading cause of death from malignant diseases worldwide in spite of the advances in surgical treatment and multimodality treatments (Hibi*, et al.*, 1998).

Cancer stem cells have attributed resistance of a smaller fraction of cells in the tumor bulk against chemotherapeutics. The isolation of CSCs is important for these reasons and have been isolated using a variety of stem cell markers and phenotypes. CD133 has recently been reported to identify tumor-initiating cells in non-small cell lung cancer (NSCLC). ABCG2 is also a stem cell marker of a variety of tissues and transporter responsible for the multidrugresistance phenotype. However, it was demonstrated that many cells in NSCLC and SCLC cell lines show tumorigenic potential, regardless of ABCG2 and CD133 expression. Recently, ALDH activity has been used for isolation of these kinds of cells. Normal SCs were shown to contain higher levels of ALDH activity than their more differentiated progeny. ALDHpositive cells of tumors have higher proliferation rates, migration and adhesion ability, and metastatic potential than ALDH-negative cells. This may occur because that RA product of ALDHs is thought to participate in cellular differentiation and stem cell self-protection (Serrano*, et al.*, 2011).
