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In vitro radiotherapy and chemotherapy alter migration of brain cancer cells before cell death.

ABSTRACT: Although radiotherapy and most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis strategies alongside chemotherapy and radiotherapy. An important step in the metastatic cascade is migration. It is the first step in metastasis via local invasion. Here we address the question whether ionizing radiation and/or chemotherapy might inadvertently promote metastasis and/or invasiveness by enhancing cell migration. We used a standard laboratory irradiator, Faxitron CellRad, to irradiate both non-cancer (HCN2 neurons) and cancer cells (T98G glioblastoma) with 2 Gy, 10 Gy and 20 Gy of X-rays. Paclitaxel (5 μM) was used for chemotherapy. We then measured the attachment and migration of the cells using an electric cell substrate impedance sensing device. Both the irradiated HCN2 cells and T98G cells showed significantly (p < 0.01) enhanced migration compared to non-irradiated cells, within the first 20-40 h following irradiation with 20 Gy. Our results suggest that cell migration should be a therapeutic target in anti-metastasis/anti-invasion strategies for improved radiotherapy and chemotherapy outcomes.

SUBMITTER: Merrick M

PROVIDER: S-EPMC8280507 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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In vitro radiotherapy and chemotherapy alter migration of brain cancer cells before cell death.

Merrick Michael M Mimlitz Michael J MJ Weeder Catherine C Akhter Haris H Bray Allie A Walther Andrew A Nwakama Chisom C Bamesberger Joe J Djam Honour H Abid Kaamil K Ekpenyong Andrew A

Biochemistry and biophysics reports 20210713

Although radiotherapy and most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis strategies alongside chemotherapy and radiotherapy. An important step in the metastatic cascade is migration. It is the first step in metastasis via local invasi ...[more]

PMID: 34286111

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Project description:BackgroundGlioblastoma (GBM) is an aggressive therapy-resistant brain tumour that may impacts the integrity of the blood-brain barrier (BBB). The BBB is a protective barrier of the central nervous system formed mainly by endothelial cells. This study aimed to investigate the in vitro effect of GBM cells on the BBB.MethodsBrain endothelial (bEnd.3) cells were used as a model of the BBB. Glioblastoma-conditioned media (CM) was extracted at the 48-h (h) time-point from the U87 GBM cells and diluted to 40% with fresh media. The effect of the U87-CM collected at 48 h on bEnd.3 cell growth was evaluated following 48 and 72 h of treatment using the xCELLigence system. Additionally, bEnd.3 cell growth was also investigated in a U87 and bEnd.3 co-culture model continuously for 48 h using the xCELLigence system. The migration of bEnd.3 cells was assessed following 48 and 72 h using the migration scratch assay. The barrier integrity was evaluated continuously for 1 h using the transwell permeability, and the tight junction (TJ) protein expression was evaluated using Western blot assay following 48 and 72 h.ResultsThere was a significant decrease in bEnd.3 cell growth following 32 h (p < 0.05), 40 h (p < 0.01), and 48 h (p < 0.001) of treatment with U87-CM, while co-culturing of bEnd.3 and U87 cells increased cell growth following 16 h (p < 0.05), 24 h (p < 0.001), 32 h (p < 0.01), 40 h (p < 0.001), and 48 h (p < 0.001). The migration of bEnd.3 cells significantly increased following both 24 (p < 0.05) and 48 h (p < 0.01) of treatment with U87-CM. The permeability of bEnd.3 cells co-cultured with U87 for 48 h was significantly increased (p < 0.05) at the 15- and 30-min time points. Furthermore, the expression of ZO-1 and occludin was significantly increased (p < 0.05) in both bEnd.3 cells treated with U87-CM as well as bEnd.3 cells co-cultured with U87 cells.ConclusionThe current findings suggest that U87 cells alter the integrity of bEnd.3 cells possibly through the secretomes in the CM and through cell-cell interactions in co-culture models. This may assist in the understanding of the mechanisms by which GBM affects the BBB, which may aid in the management thereof.

Project description:ObjectiveIt is unclear how to best sequence adjuvant chemotherapy and radiotherapy for advanced endometrial cancer. We studied the outcomes for women treated with chemotherapy before radiotherapy in a chemotherapy-first (chemotherapy for 6 cycles followed radiotherapy) or 'sandwich' approach (chemotherapy for 3 cycles followed by radiotherapy and subsequently chemotherapy for 3 cycles).MethodsWomen with stage IIIC endometrial cancer and no gross residual disease treated with chemotherapy before radiotherapy between April 2003 and April 2016 were included. The Kaplan-Meier method was used to estimate recurrence and survival. We performed a meta-analysis of endometrial cancer trials comparing chemotherapy and radiotherapy versus radiotherapy alone.ResultsA total of 102 patients were included. The mean (SD) age was 63.8 (10.6) years; 84 patients received the chemotherapy-first approach and 18 patients received the 'sandwich' approach. Pelvic and para-aortic nodes were removed in 99% and 88.2%, respectively. Among all the patients, we observed 1 pelvic (1%), 1 para-aortic (1%), and 5 vaginal (4.9%) recurrences. At 3 years, for the 'sandwich' and chemotherapy-first approaches, the vaginal recurrence was 11.8% and 4.2%, pelvic recurrence was 0% and 1.5%, para-aortic recurrence was 0% and 1.2%, distant recurrence was 42.9% and 24.4%, and overall survival was 70.3% and 81.7%, respectively. With 'chemotherapy before radiotherapy' 94.9% completed 4+ chemotherapy cycles (vs 71-90% reported in the literature for 'radiotherapy before chemotherapy'). In a meta-analysis of endometrial cancer trials, distant recurrence rates were reduced with 4+ chemotherapy cycles but not with 3 cycles (p=0.01).ConclusionChemotherapy before radiation sequencing for stage IIIC endometrial cancer was associated with a high proportion of patients completing 4+ chemotherapy cycles and low locoregional lymphatic recurrence rate, despite delaying radiotherapy until after 3-6 cycles of chemotherapy and not administering concurrent cisplatin.

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In vitro radiotherapy and chemotherapy alter migration of brain cancer cells before cell death.

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In vitro radiotherapy and chemotherapy alter migration of brain cancer cells before cell death.

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