Human Lung Cancer cell line SPC-A1 contains cells with characteristics of cancer stem cells

Abstract

Cancer stem cells (CSCs) play important roles in occurrence, development, recurrence and metastasis of cancer. Isolation and identification of CSCs have been performed from some cancer tissues or cells. In this paper, human lung adenocarcinoma stem cells were induced and isolated from SPC-A1 cells and their characteristics were determined. SPC-A1 cells were cultured in serum-free medium and epidermal growth factor and basic fibroblast growth factor were added into the medium to induce the formation of multicellular tumor spheroids. The results showed that floating multicellular tumor spheroids (named pulmospheres) were formed 5-10 d after the induction of SPC-A1 cells. Real-time PCR analysis showed that in the pulmospheres, the marker of bronchioalveolar stem cells, Clara cell secretary protein and the marker of AT2 cells, alveolar surfactant protein C were highly expressed. Furthermore, such embryonic stem cell markers as octamer-binding transcription factor 4 (OCT-4), Bmi-1, and thyroid transcription factor -1 (TTF-1) were also highly expressed. Some miRNAs as hsa-miR-126, hsa-miR-145, hsa-let-7g, hsa-let-7d, hsa-let-7c, hsa-let-7e and hsa-miR-98, which were lowly expressed in SPC-A1 cells, were not expressed in the pulmospheres. Cell cycle analysis showed that 94.29 % of the pulmosphere cells were in G1 stages. Further study showed that these cells possessed higher proliferation and invasion activity than SPC-A1 cells. Tumorigenicity activity experiments on BALB/c nude mice showed that 1 × 103 of the pulmosphere cells could form tumors with similar pathological features with lung adenocarcinoma. In conclusion, lung adenocarcinoma stem cells were enriched in the pulmosphere cells and were with high tumorigenicity.

Three‐dimensional cell culture model utilization in cancer stem cell research

“…This model has been used to study the expression profile of stem cell signalling in CD133 high /CD44 high prostate cancer stem cells and glioblastoma tumor‐initiating cells (Oktem et al , ). Additionally, this technique has demonstrated that human lung cancer cell line SPC‐A1 contains a subpopulation of CSCs (Zhou, Yang & Li, ).…”

miR-145-5p Targets Sp1 in Non-Small Cell Lung Cancer Cells and Links to BMI1 Induced Pemetrexed Resistance and Epithelial–Mesenchymal Transition

“…In A549 cells, the expression of miR-145-5p was suppressed when BMI1 was highly expressed ( Figure 4 B). It has been found that the expression of miR-145 was negatively correlated with high expression of BMI1 in CSCs derived from SPC-A1 lung cancer cells [ 37 ]. In colorectal cancer cells, epigallocatechin-3-gallate, a polyphenol phytochemical, was discovered to inhibit the expression of Notch, BMI1, and EZH2 with an upregulation of the expression of miR-145, miR-34a, and miR-200c, thus reducing tumor growth [ 38 ].…”

Abnormal activation of the EGFR signaling pathway mediates the downregulation of miR-145 through the ERK1/2 in non-small cell lung cancer

“…It has been confirmed that miR-145 has a tumor suppressor function (22,23). miR-145 had a lower level of expression in lung, breast, prostate and colorectal cancer cells (24)(25)(26). However, it is unclear why miR-145 is downregulated in these tumor cells.…”