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Rath et al. J Cancer Metastasis Treat 2020;6:30 I http://dx.doi.org/10.20517/2394-4722.2020.51 Page 5 of 10

Figure 3. Cytotoxicity test of BHGc10 SCLC CTCs employing topotecan showing the control and MAT supplementation, respectively
(Error bars represent mean values ± SD). For this experiment MAT was pretreated with a freeze-thaw cycle. CTCs: circulating tumor
cells; SCLC: small-cell lung cancer; MAT: material

Results of the chemosensitivity tests are summarized in Figure 4. Of the nine cell lines shown, only
SCLC26A is derived from a pleural effusion and this demonstrated a decreased chemosensitivity to
topotecan in the presence of MAT. All other cell lines exhibited increased resistance upon inclusion of
MAT, including pleural cell line S457 and established cell lines NCI-69, NCI-H417 and DMS153.

Size distribution of MAT
MAT was analyzed for size distribution of its fragments and their appearances using SEM [Figure 5]. The
results for BHGc7 CTCs show a continuous decrease in the size of their cellular fragments ranging from
fully intact cells (10-12 µm) down to small sizes of approximately 2 µm. SEM also demonstrated that the
cellular fragments exhibit a range of sizes and an appearance of degraded cells with remaining cytoskeletal
structures.

For BHGc7, a wide range of cancer-related proteins were compared between the native cell line and MAT
release. We used the ARY026 Proteome Profiler Array because in this particular cell line, its cell fragments
demonstrate intact membranes in the beginning [Figure 6]. Although there was some variability in the
expression of proteins, markers including p53, Enolase-2 and EpCAM were preserved upon release of the
fragments. In general, MAT represents the normal cellular protein content of the cell of origin as far as
testing with this specific array.

DISCUSSION
The prognosis of SCLC has not improved significantly in recent times despite the introduction of novel
[2,3]
therapeutics and immunotherapy . The addition of anti-PD-L1 atezolizumab to chemotherapy for ED-
SCLC has increased the median overall survival by 2 months and the median progression-free survival