Aggressive phenotype of cells disseminated via hematogenous and lymphatic route in breast cancer patients
Aleksandra Markiewicz , Anna Nagel , Jolanta Szade , Hanna Majewska , Jarosław Skokowski , Barbara Seroczynska , Tomasz Stokowy , Marzena Wełnicka-Jaśkiewicz , Anna Żaczek
AbstractIntratumoral heterogeneity of breast cancer remains a major challenge in successful treatment. Failure of cancer therapies can also be accredited to inability to systemically eradicate cancer stem cells (CSCs). Recent evidence points to the role of epithelial-mesenchymal transition (EMT) in expanding the pool of tumor cells with CSCs features. Thus, we assessed expression level as well as heterogeneity of CSCs markers in primary tumors (PT), lymph node metastasis (LNM), and circulating tumor cells (CTCs)–enriched blood fractions in order to correlate them with signs of EMT activation as well as clinicopathological data of breast cancer patients. Level of CSCs markers (ALDH1, CD44, CD133, OCT-4, NANOG) and EMT markers was quantified in PT (N=107), LNM (N=56), and CTCs-enriched blood fractions (N=85). Heterogeneity of CSCs markers expression within each PT and LNM was assessed by calculating Gini Index. Percentage of ALDH1-positive cells was elevated in PT in comparison to LNM (P = .005). However, heterogeneity of the four CSCs markers: ALDH1 (P = .019), CD133 (P = .009), OCT-4 (P = .027), and CD44 (P < .001) was decreased in LNM. Samples classified as mesenchymal (post-EMT) showed elevated expression of CSCs markers (OCT-4 and CD44 in PT; OCT-4 in LNM; ALDH1, OCT-4, NANOG, CD44 in CTCs). Patients with mesenchymal-like CTCs had worse prognosis than patients with epithelial-like or no CTCs (P = .0025). CSCs markers are enriched in PT, LNM, and CTCs with mesenchymal features, but their heterogeneity is decreased in metastatic lymph nodes. Mesenchymal CTCs phenotype correlates with poor prognosis of the patients.
|Journal series||Translational Oncology, ISSN 1944-7124, e-ISSN 1936-5233, (A 25 pkt)|
|Publication size in sheets||0.5|
|License||Journal (articles only); published final; ; with publication|
|Score|| = 25.0, 31-10-2018, ArticleFromJournal|
= 30.0, 31-10-2018, ArticleFromJournal
|Publication indicators||: 2016 = 3.025 (2) - 2016=3.225 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.