CoChat
Sign Up
Cited by 15Mesenchymal stem cell researchProstate Cancer Treatment and ResearchCancer Cells and Metastasis

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression

Open access
Sousa, André, Coelho, Pedro, Leite, Fernanda, Teixeira, Catarina, Rocha, Ana Catarina, Santos, Inês, Baylina, Pilar, Fernandes, Ruben, Soares, Raquel, Costa, Raquel, Gomes, Andreia·2023·Human Cell
DOI 10.1007/s13577-023-00880-zPMC PMC10110723
Open this paper in CoChat — free accountOpen PDF

Abstract

Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa. Graphical abstract

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s13577-023-00880-z

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Functional assays under UC-MSC secretome. A Cytotoxicity rate in HPEpiC, PC3 and LNCaP cell lines and B proliferation rate in HPEpiC, PC3 and LNCaP cell lines for 0%, 25%, 50%, 75% and 100% UC-MSC secretome concentration. C Motility rate in HPEpiC, PC3 and LNCaP cell lines in the UC-MSC secretome concentration of 100%. D Migratory evaluation of HPEpiC, PC3 and LNCaP cell lines in the UC-MSC secretome concentration of 100%. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001)
Fig. 1 Functional assays under UC-MSC secretome. A Cytotoxicity rate in HPEpiC, PC3 and LNCaP cell lines and B proliferation rate in HPEpiC, PC3 and LNCaP cell lines for 0%, 25%, 50%, 75% and 100% UC-MSC secretome concentration. C Motility rate in HPEpiC, PC3 and LNCaP cell lines in the UC-MSC secretome concentration of 100%. D Migratory evaluation of HPEpiC, PC3 and LNCaP cell lines in the UC-MSC secretome concentration of 100%. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001)CC BY · PubMed Central
Fig. 2 Functional assays under CBS concentrations. A Cytotoxicity rate in HPEpiC, PC3 and LNCaP cell lines. B Proliferation rate in HPEpiC, PC3 and LNCaP cell lines. C Motility rate in HPEpiC, PC3 and LNCaP cell lines in the CBS concentration of 10%. D Migratory evaluation of HPEpiC, PC3 and LNCaP cell lines in the CBS concentration of 10%. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001)
Fig. 2 Functional assays under CBS concentrations. A Cytotoxicity rate in HPEpiC, PC3 and LNCaP cell lines. B Proliferation rate in HPEpiC, PC3 and LNCaP cell lines. C Motility rate in HPEpiC, PC3 and LNCaP cell lines in the CBS concentration of 10%. D Migratory evaluation of HPEpiC, PC3 and LNCaP cell lines in the CBS concentration of 10%. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001)CC BY · PubMed Central
Fig. 3 Gene relative quantification in HPEpiC, PC3 and LNCaP cell lines. A AKT. B PI3K. C p53. D IL-1β. E IL-6. F IL-10. Bars colors in (A)–(E) represents studied groups: groups: Control group; 100% of UC-MSC; 10% of CBS. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01)
Fig. 3 Gene relative quantification in HPEpiC, PC3 and LNCaP cell lines. A AKT. B PI3K. C p53. D IL-1β. E IL-6. F IL-10. Bars colors in (A)–(E) represents studied groups: groups: Control group; 100% of UC-MSC; 10% of CBS. Symbols above bars represent statistical significance (*p < 0.05; **p < 0.01)CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 51

  1. Rawla P. Epidemiology of prostate cancer. World J Oncol Elmer Press. 2016;10:107–25.
  2. Sharp VJ, Takacs EB, Powell CR. Prostatitis: diagnosis and treatment. Am Fam Physician. 2010;82(4):397–406.
  3. Bachmann C. Serenoa repens for benign prostatic hyperplasia. Schweiz Z für Ganzheitsmed/Swiss J Integr Med. 2015;27(4):202–6. · DOI
  4. Hulvat MC. Cancer incidence and trends. Surg Clin North Am. 2020;100(3):469–81. · DOI
  5. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. · DOI · Paper page
  6. Rahimi Tesiye M, Abrishami Kia Z, Rajabi-Maham H. Mesenchymal stem cells and prostate cancer: a concise review of therapeutic potentials and biological aspects. Stem Cell Res. 2022;63: 102864. · DOI
  7. Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA. 2017;317(24):2532–42. · DOI
  8. Abbasian Ardakani A, Rajaee J, Khoei S. Diagnosis of human prostate carcinoma cancer stem cells enriched from DU145 cell lines changes with microscopic texture analysis in radiation and hyperthermia treatment using run-length matrix. Int J Radiat Biol. 2017;93(11):1248–56. · DOI
  9. Driscoll J, Patel T. The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease. J Gastroenterol. 2019;54(9):763–73. · DOI
  10. Liau LL, et al. Characteristics and clinical applications of Wharton’s jelly-derived mesenchymal stromal cells. Curr Res Transl Med. 2020;68(1):5–16. · DOI
  11. Subramanian A, et al. Comparative characterization of cells from the various compartments of the human umbilical cord shows that the Wharton’s jelly compartment provides the best source of clinically utilizable mesenchymal stem cells. PLoS ONE. 2015;10(6): e0127992. · DOI
  12. Gomes A, et al. Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach. Cell Tissue Res. 2021;385(3):497–518. · DOI
  13. Shojaei S, et al. Effect of mesenchymal stem cells-derived exosomes on tumor microenvironment: tumor progression versus tumor suppression. J Cell Physiol. 2019;234(4):3394–409. · DOI
  14. Sandonà M, et al. Mesenchymal stromal cells and their secretome: new therapeutic perspectives for skeletal muscle regeneration. Front Bioeng Biotechnol. 2021;9: 652970. · DOI
  15. Noiseux N, et al. Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther. 2006;14(6):840–50. · DOI
  16. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84. · DOI · Paper page
  17. Yeo RWY, et al. Exosome: a novel and safer therapeutic refinement of mesenchymal stem cell. J Circulating Biomark. 2013. https://doi.org/10.5772/57460. · DOI
  18. Bian D, et al. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review. Stem Cell Res Ther. 2022;13(1):24. · DOI
  19. Salgado AJ, et al. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010;5(2):103–10. · DOI
  20. Liu CB, et al. Human umbilical cord-derived mesenchymal stromal cells improve left ventricular function, perfusion, and remodeling in a porcine model of chronic myocardial ischemia. Stem Cells Transl Med. 2016;5(8):1004–13. · DOI
  21. Si Y, et al. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes. 2012;61(6):1616–25. · DOI
  22. Soria B, et al. Human mesenchymal stem cells prevent neurological complications of radiotherapy. Front Cell Neurosci. 2019;13:204. · DOI
  23. Song JY, et al. Umbilical cord-derived mesenchymal stem cell extracts ameliorate atopic dermatitis in mice by reducing the T cell responses. Sci Rep. 2019;9(1):6623. · DOI
  24. Eleuteri S, Fierabracci A. Insights into the secretome of mesenchymal stem cells and its potential applications. Int J Mol Sci. 2019;20(18):4597. · DOI
  25. Park CW, et al. Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int J Stem Cells. 2009;2(1):59–68. · DOI
  26. Zhang LN, et al. Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells. J Cell Physiol. 2019;234(4):3570–82. · DOI
  27. Melzer C, von der Ohe J, Hass R. In vivo cell fusion between mesenchymal stroma/stem-like cells and breast cancer cells. Cancers. 2019;11(2):185. · DOI
  28. Hmadcha A, et al. Therapeutic potential of mesenchymal stem cells for cancer therapy. Front Bioeng Biotechnol. 2020. https://doi.org/10.3389/fbioe.2020.00043. · DOI
  29. Lu L, et al. Bone marrow mesenchymal stem cells suppress growth and promote the apoptosis of glioma U251 cells through downregulation of the PI3K/AKT signaling pathway. Biomed Pharmacother. 2019;112: 108625. · DOI
  30. Ho IA, et al. Human bone marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesis. Stem Cells. 2013;31(1):146–55. · DOI
  31. Lee C, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126(22):2601–11. · DOI
  32. Pakravan K, et al. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cell Oncol (Dordr). 2017;40(5):457–70. · DOI
  33. Belderbos ME, et al. Plasma-mediated immune suppression: a neonatal perspective. Pediatr Allergy Immunol. 2013;24(2):102–13. · DOI
  34. Cox ST, et al. Functional characterisation and analysis of the soluble NKG2D ligand repertoire detected in umbilical cord blood plasma. Front Immunol. 2018;9:1282. · DOI
  35. Samarkanova D, et al. Cord blood platelet rich plasma derivatives for clinical applications in non-transfusion medicine. Front Immunol. 2020;11:942. · DOI
  36. Solves P, et al. Qualitative and quantitative cell recovery in umbilical cord blood processed by two automated devices in routine cord blood banking: a comparative study. Blood Transfus. 2013;11(3):405–11.
  37. Cervantes-Villagrana RD, et al. Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies. Signal Transduct Target Ther. 2020;5(1):99. · DOI
  38. Park S, et al. PI3K pathway in prostate cancer: all resistant roads lead to PI3K. Biochim Biophys Acta Rev Cancer. 2018;1870(2):198–206. · DOI
  39. Whiteside TL. Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment. Semin Immunol. 2018;35:69–79. · DOI
  40. Dabrowski FA, et al. Comparison of the paracrine activity of mesenchymal stem cells derived from human umbilical cord, amniotic membrane and adipose tissue. J Obstet Gynaecol Res. 2017;43(11):1758–68. · DOI
  41. Sun X, et al. Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation in type 2 diabetes rats. Stem Cell Res Ther. 2017;8(1):241. · DOI
  42. Yao J, et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. Faseb j. 2019;33(2):1695–710. · DOI
  43. Versura P, et al. Efficacy of standardized and quality-controlled cord blood serum eye drop therapy in the healing of severe corneal epithelial damage in dry eye. Cornea. 2013;32(4):412–8. · DOI
  44. Riquelme I, et al. The gene expression status of the PI3K/AKT/mTOR pathway in gastric cancer tissues and cell lines. Pathol Oncol Res. 2016;22(4):797–805. · DOI
  45. Zhou J, et al. Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library. BMC Med Genom. 2012;5:34. https://doi.org/10.1186/1755-8794-5-34. · DOI
  46. Creighton CJ, et al. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res. 2010;12(3):R40. · DOI
  47. Dasu MR, Devaraj S, Jialal I. High glucose induces IL-1beta expression in human monocytes: mechanistic insights. Am J Physiol Endocrinol Metab. 2007;293(1):E337–46. · DOI
  48. Chen MF, et al. Role of interleukin 1 beta in esophageal squamous cell carcinoma. J Mol Med (Berl). 2012;90(1):89–100. · DOI
  49. Kai H, et al. Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res. 2005;25(2a):709–13.
  50. Deans DA, et al. Elevated tumour interleukin-1beta is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer. Br J Cancer. 2006;95(11):1568–75. · DOI
  51. Jiang XP, et al. Down-regulation of expression of interleukin-6 and its receptor results in growth inhibition of MCF-7 breast cancer cells. Anticancer Res. 2011;31(9):2899–906.

Cited by

Sorted by citations

See all 15

Metadata

Authors
Sousa, A., Coelho, P., Leite, F., Teixeira, C., Rocha, A. C., Santos, I., Baylina, P., Fernandes, R., Soares, R., Costa, R., & Gomes, A.
Affiliations
Universidade do Porto (PT)
Corresponding author
Gomes, Andreia
ORCID
Venue
Human Cell
Publisher
Springer Science and Business Media LLC
Published
2023-02-19
Volume
36
Issue
3
Pages
1160-1172
ISSN
  • 0914-7470 (ISSN-L)
  • 1749-0774
DOI
10.1007/s13577-023-00880-z
PMC
PMC10110723
OpenAlex
W4321366474
Cited by
15
References
2
Citations by year
2026: 2 · 2025: 4 · 2024: 7 · 2023: 2
FWCI
2.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Human Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
Funders
  • Bebé Vida - Ciências Para A Vida, S.A
  • Fundação para a Ciência e a Tecnologia (UID/BIM/0493/2020, 2021.06521.BD)
  • Instituto Politécnico do Porto (IPP4COVID/BI/02/2020)
  • Porto Research, Technology & Innovation Center (PORTIC/LabMi/BI/2021/03)
  • Universidade do Porto
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
prostate cancer, human umbilical cord mesenchymal stem cells, MSC secretome, cord blood serum, tumor progression, PI3K/Akt signaling, p53, interleukin genes, anti-inflammatory factors, cell proliferation, cell motility, PC-3 cells, LNCaP cells, cancer stem cells
MeSH terms
Secretome, Humans, Male, Prostate, Prostatic Neoplasms, Stem Cells, Umbilical Cord, Tumor Suppressor Protein p53, Phosphatidylinositol 3-Kinases, Serum, Proto-Oncogene Proteins c-akt

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review