Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Błogowski, Wojciech; Bodnarczuk, Tomasz; Starzyńska, Teresa

doi:10.5966/sctm.2015-0291

Cited by 28 publications

(26 citation statements)

References 89 publications

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“…The growth and progression of cancer cells require the support from the Paradoxically, such capacities also facilitate tumor cell survival. Although majority of studies support MSCs can accelerate the growth and progression of tumor [4][5][6][7], however, anti-cancer effects were also observed in other studies [8][9][10]. Our group also demonstrated that under specific circumstances such as post chemotherapy, MSCs can switch phenotype and becomes an anti-cancer factor.…”

Section: Introductionsupporting

confidence: 47%

“…Majority of studies observed the supportive effects of cotransplanted MSCs on cancers using excessive number of MSCs than cancer cells or at least an equal number. Specially, my study validated that lower dosage of MSCs co-injection using 0.5⋅10 5 MSCs and 1⋅10 5 neuroblastoma cells was enough to generate the promoting effects on tumor growth and metastasis. However, much lower dosage of MSCs (10 2 MSCs to 10 4 cancer cells) was found to induce tumor rejection [23].…”

Section: Discussionmentioning

confidence: 58%

“…Until now, the exact impact of MSCs on tumor growth and progression in vivo is still controversial. The favorable effects of MSCs have been reported in the tumorigenesis of ovarian cancer [12], colorectal carcinoma [13], breast cancer [4] and pancreatic cancer [5] Moreover, MSCs protect cancer cell survival from cytotoxicity of anti-cancer reagents [16]. However, MSCs also exerted negative effects on the growth of colon carcinoma [17], Kaposi's carcinoma [18], glioma [9] and hepatoma model [8].…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic lociin orthotopic neuroblasoma model

CHAN

Chan

2020

Preprint

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Background Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. Methods In our study, an orthotopic neuroblasoma murine model was utilized to mimic the actual scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without MSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of MSCs towards tumor was analyzed by tracing fluorescence signal tagged on MSCs using CRI maestroTM imaging system. Results hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the metastatic loci. The metastatic potential was significantly reduced when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was a prime mover in the metastatic process. Conclusions MSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of MSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered MSCs as vehicles for targeted anti-cancer therapy against advanced cancers.

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Section: Introductionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic lociin orthotopic neuroblasoma model

CHAN

Chan

2020

Preprint

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“…Besides, recent studies by Blogowski et al . [ 6 , 7 ] found abnormal peripheral trafficking of bone marrow-derived stem cells in patients with gastric cancer but absent in other types of gastric neoplasms and healthy individuals, hence highlighting the potential of using these circulating bone marrow-derived stem cells as a biomarker. These liquid biopsies approaches may represent a valid alternative to tumor biopsies that are invasive, painful and provide only information for a small region of a tumor at a single time point.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of circulating colorectal tumor cells defines genetic signatures for individualized cancer care

et al. 2017

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Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples. We developed an analysis pipeline to minimize false-positive detection of somatic mutations in amplified DNA. In 60% of the CTC-enriched blood samples, we detected primary tumor matching mutations. We found a significant positive correlation between the allele frequencies of somatic mutations detected in CTCs and abnormal CEA serum level. Strikingly, we found driver mutations and amplifications in cancer and druggable genes such as APC, KRAS, TP53, ERBB3, FBXW7 and ERBB2. In addition, we found that CTCs carried mutation signatures that resembled the signatures of their primary tumors. Cumulatively, our study defined genetic signatures and somatic mutation frequency of colorectal CTCs. The identification of druggable mutations in CTCs of preoperative colorectal cancer patients could lead to more timely and focused therapeutic interventions.

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“…Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent stem cells capable of differentiating into numerous cell types, including fibroblasts, as well as cartilage, bone, muscle and brain cells ( 23 – 26 ). They secrete a large number of growth factors and cytokines that are critical for the repair of injured tissues ( 23 , 24 , 27 ). In this study, we determined whether SUMOs and the SUMO cycle are involved in the effects of hypothermia on BMSCs and their role in an adverse environment.…”

Section: Introductionmentioning

confidence: 99%

Hypothermia inhibits the proliferation of bone marrow-derived mesenchymal stem cells and increases tolerance to hypoxia by enhancing SUMOylation

et al. 2017

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Hypothermia therapy has a positive effect on patients with severe brain injury. Recent studies have shown that mild hypothermia increases the survival of bone marrow-derived mesenchymal stem cells (BMSCs) in a hypoxic environment; however, the underlying mechanisms are not yet fully understood. Small ubiquitin-like modifiers (SUMOs) are sensitive to temperature stress reactions and are considered to exert a protective effect. In this study, we examined the protective effects of hypothermia on BMSCs in terms of SUMO protein modification. First, we found that mild hypothermia inhibited the proliferation and differentiation of BMSCs and increased cell tolerance to a hypoxic environment. Second, hypothermia significantly increased the levels of SUMO modification of multiple proteins in BMSCs. The knockdown of SUMO1/2/3 induced the rapid aging of the BMSCs, while the inhibition of the SUMO-conjugating enzyme, Ubc9, reduced cell proliferation and increased the proportion of BMSCs differentiating into nerve cells. Moreover, the tolerance of BMSCs to the hypoxic environment was significantly decreased. Lastly, we investigated 4 reported SUMO target proteins, anti-proliferating cell nuclear antigen, octamer-binding transcription factor 4, p53 and hypoxia-inducible factor-1α, to confirm that SUMO modification was indeed involved in maintaining the proliferation, inhibiting differentiation and enhancing the resistance of BMSCs against adverse conditions. Taken together, our results indicate that the SUMO pathway is involved in the response to hypothermic stress, and that SUMOylation may be an important protective mechanism against hypothermia for the survival of BMSCs under unfavorable conditions.

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Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

Cited by 28 publications

References 89 publications

Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic lociin orthotopic neuroblasoma model

Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic lociin orthotopic neuroblasoma model

Molecular characterization of circulating colorectal tumor cells defines genetic signatures for individualized cancer care

Hypothermia inhibits the proliferation of bone marrow-derived mesenchymal stem cells and increases tolerance to hypoxia by enhancing SUMOylation

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