open access

Vol 62, No 1 (2024)
Original paper
Submitted: 2023-12-04
Accepted: 2024-03-28
Published online: 2024-04-04
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Effects of bone marrow mesenchymal stem cell-conditioned medium on the proliferation and migration of liposarcoma cells

Hua Chen1, Na Sha1, Ning Liu1, Haijun Hu2
·
Pubmed: 38639334
·
Folia Histochem Cytobiol 2024;62(1):50-60.
Affiliations
  1. Department of Emergency, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, Guangdong, China
  2. Department of Gastrointestinal surgery, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, Guangdong, China

open access

Vol 62, No 1 (2024)
ORIGINAL PAPERS
Submitted: 2023-12-04
Accepted: 2024-03-28
Published online: 2024-04-04

Abstract

Introduction. Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells.

Materials and methods. We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay.

Results. Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression.

Conclusions. These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.

Abstract

Introduction. Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells.

Materials and methods. We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay.

Results. Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression.

Conclusions. These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.

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Keywords

human BMSC; conditioned medium; liposarcoma; proliferation; migration; YAP1 silencing

About this article
Title

Effects of bone marrow mesenchymal stem cell-conditioned medium on the proliferation and migration of liposarcoma cells

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 62, No 1 (2024)

Article type

Original paper

Pages

50-60

Published online

2024-04-04

Page views

183

Article views/downloads

84

DOI

10.5603/fhc.98379

Pubmed

38639334

Bibliographic record

Folia Histochem Cytobiol 2024;62(1):50-60.

Keywords

human BMSC
conditioned medium
liposarcoma
proliferation
migration
YAP1 silencing

Authors

Hua Chen
Na Sha
Ning Liu
Haijun Hu

References (63)
  1. Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica. 2021; 113(2): 70–84.
  2. Schöffski P. Established and experimental systemic treatment options for advanced liposarcoma. Oncol Res Treat. 2022; 45(9): 525–543.
  3. Bonvalot S, Gronchi A, Le Péchoux C, et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020; 21(10): 1366–1377.
  4. Callegaro D, Raut CP, Ajayi T, et al. Preoperative radiotherapy in patients with primary retroperitoneal sarcoma: EORTC-62092 trial (STRASS) versus off-trial (STREXIT) results. Ann Surg. 2023; 278(1): 127–134.
  5. Erstad DJ, Chiang YJ, Witt RG, et al. Clinical impact of external beam radiotherapy for surgically resected primary retroperitoneal liposarcoma. Ann Surg Oncol. 2023; 30(2): 926–940.
  6. von Mehren M, Kane JM, Agulnik M, et al. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20(7): 815–833.
  7. Stacchiotti S, Van der Graaf WTA, Sanfilippo RG, et al. First-line chemotherapy in advanced intra-abdominal well-differentiated/dedifferentiated liposarcoma: An EORTC Soft Tissue and Bone Sarcoma Group retrospective analysis. Cancer. 2022; 128(15): 2932–2938.
  8. Schöffski P, Grignani G, Blay JY, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016; 387(10028): 1629–1637.
  9. Patel S, von Mehren M, Reed DR, et al. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019; 125(15): 2610–2620.
  10. Gleason CE, Dickson MA, Klein Dooley ME, et al. Therapy-induced senescence contributes to the efficacy of abemaciclib in patients with dedifferentiated liposarcoma. Clin Cancer Res. 2024; 30(4): 703–718.
  11. Abdul Razak AR, Bauer S, Suarez C, et al. Co-Targeting of MDM2 and CDK4/6 with siremadlin and ribociclib for the treatment of patients with well-differentiated or dedifferentiated liposarcoma: results from a proof-of-concept, phase ib study. Clin Cancer Res. 2022; 28(6): 1087–1097.
  12. Kyriazoglou A, Gkaralea LE, Kotsantis I, et al. Tyrosine kinase inhibitors in sarcoma treatment. Oncol Lett. 2022; 23(6): 183.
  13. Blay JY, Chevret S, Le Cesne A, et al. Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial. Lancet Oncol. 2023; 24(8): 892–902.
  14. Gounder MM, Razak AA, Somaiah N, et al. Selinexor in advanced, metastatic dedifferentiated liposarcoma: a multinational, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2022; 40(22): 2479–2490.
  15. Li X, Fan Q, Peng X, et al. Mesenchymal/stromal stem cells: necessary factors in tumour progression. Cell Death Discov. 2022; 8(1): 333.
  16. Slama Y, Ah-Pine F, Khettab M, et al. The dual role of mesenchymal stem cells in cancer pathophysiology: pro-tumorigenic effects versus therapeutic potential. Int J Mol Sci. 2023; 24(17).
  17. Rodriguez R, Tornin J, Suarez C, et al. Expression of FUS-CHOP fusion protein in immortalized/transformed human mesenchymal stem cells drives mixoid liposarcoma formation. Stem Cells. 2013; 31(10): 2061–2072.
  18. Kim YuJ, Kim M, Park HK, et al. Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology. Lab Invest. 2019; 99(9): 1309–1320.
  19. Jo EB, Lee H, Lee KW, et al. Complete regression of metastatic de-differentiated liposarcoma with engineered mesenchymal stromal cells with dTRAIL and HSV-TK. Am J Transl Res. 2020; 12(7): 3993–4000.
  20. Pocaterra A, Romani P, Dupont S. YAP/TAZ functions and their regulation at a glance. J Cell Sci. 2020; 133(2).
  21. Piccolo S, Panciera T, Contessotto P, et al. YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches. Nat Cancer. 2023; 4(1): 9–26.
  22. Trautmann M, Cheng YY, Jensen P, et al. Requirement for YAP1 signaling in myxoid liposarcoma. EMBO Mol Med. 2019; 11(5).
  23. Morice S, Mullard M, Brion R, et al. The YAP/TEAD axis as a new therapeutic target in osteosarcoma: effect of verteporfin and CA3 on primary tumor growth. Cancers (Basel). 2020; 12(12).
  24. Gao R, Kalathur RKR, Coto-Llerena M, et al. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol Med. 2021; 13(12): e14351.
  25. Lo Sardo F, Pulito C, Sacconi A, et al. YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer. Cancer Lett. 2021; 500: 51–63.
  26. Salem O, Hansen CG. The hippo pathway in prostate cancer. Cells. 2019; 8(4).
  27. Rybarczyk A, Klacz J, Wronska A, et al. Overexpression of the YAP1 oncogene in clear cell renal cell carcinoma is associated with poor outcome. Oncol Rep. 2017; 38(1): 427–439.
  28. Cha YJ, Bae SJ, Kim D, et al. High nuclear expression of yes-associated protein 1 correlates with metastasis in patients with breast cancer. Front Oncol. 2021; 11: 609743.
  29. Cymbaluk-Płoska A, Chudecka K, Chudecka-Głaz A, et al. Importance of Potential New Biomarkers in Patient with Serouse Ovarian Cancer. Diagnostics (Basel). 2021; 11(6).
  30. Zhou X, Yan Z, Hou J, et al. The Hippo-YAP signaling pathway drives CD24-mediated immune evasion in esophageal squamous cell carcinoma via macrophage phagocytosis. Oncogene. 2024; 43(7): 495–510.
  31. Ono S, Nakano K, Takabatake K, et al. Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma. Int J Med Sci. 2019; 16(5): 766–773.
  32. Cheung P, Xiol J, Dill MT, et al. Regenerative reprogramming of the intestinal stem cell state via hippo signaling suppresses metastatic colorectal cancer. Cell Stem Cell. 2020; 27(4): 590–604.e9.
  33. Yuan M, Tomlinson V, Lara R, et al. Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ. 2008; 15(11): 1752–1759.
  34. Li Xu, Zhuo S, Zhuang T, et al. YAP inhibits ERα and ER breast cancer growth by disrupting a TEAD-ERα signaling axis. Nat Commun. 2022; 13(1): 3075.
  35. Li Xu, Zhuo S, Cho YS, et al. YAP antagonizes TEAD-mediated AR signaling and prostate cancer growth. EMBO J. 2023; 42(4): e112184.
  36. Huang H, Zhang W, Pan Y, et al. YAP suppresses lung squamous cell carcinoma progression via deregulation of the dnp63-gpx2 axis and ROS accumulation. Cancer Res. 2017; 77(21): 5769–5781.
  37. Frost TC, Gartin AK, Liu M, et al. YAP1 and WWTR1 expression inversely correlates with neuroendocrine markers in Merkel cell carcinoma. J Clin Invest. 2023; 133(5).
  38. Cottini F, Hideshima T, Xu C, et al. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014; 20(6): 599–606.
  39. Maruyama J, Inami K, Michishita F, et al. Novel YAP1 activator, identified by transcription-based functional screen, limits multiple myeloma growth. Mol Cancer Res. 2018; 16(2): 197–211.
  40. Mokhtari RB, Ashayeri N, Baghaie L, et al. The hippo pathway effectors YAP/TAZ-TEAD oncoproteins as emerging therapeutic targets in the tumor microenvironment. Cancers (Basel). 2023; 15(13).
  41. Mi F, Gong L. Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma. Biosci Rep. 2017; 37(4).
  42. Meng L, Zhao Y, Bu W, et al. Bone mesenchymal stem cells are recruited via CXCL8-CXCR2 and promote EMT through TGF-β signal pathways in oral squamous carcinoma. Cell Prolif. 2020; 53(8): e12859.
  43. Pietrovito L, Leo A, Gori V, et al. Bone marrow-derived mesenchymal stem cells promote invasiveness and transendothelial migration of osteosarcoma cells via a mesenchymal to amoeboid transition. Mol Oncol. 2018; 12(5): 659–676.
  44. Huang J, Wang X, Wen J, et al. Gastric cancer cell-originated small extracellular vesicle induces metabolic reprogramming of BM-MSCs through ERK-PPARγ-CPT1A signaling to potentiate lymphatic metastasis. Cancer Cell Int. 2023; 23(1): 87.
  45. Cai X, Wang KC, Meng Z. Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression. Front Cell Dev Biol. 2021; 9: 673599.
  46. Totaro A, Panciera T, Piccolo S. YAP/TAZ upstream signals and downstream responses. Nat Cell Biol. 2018; 20(8): 888–899.
  47. Stampouloglou E, Cheng N, Federico A, et al. Yap suppresses T-cell function and infiltration in the tumor microenvironment. PLoS Biol. 2020; 18(1): e3000591.
  48. Yamaguchi H, Taouk GM. A potential role of YAP/TAZ in the interplay between metastasis and metabolic alterations. Front Oncol. 2020; 10: 928.
  49. Wang M, Zhao X, Qiu R, et al. Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a. Oncogene. 2021; 40(12): 2296–2308.
  50. Yoshida M, Horiguchi H, Kikuchi S, et al. miR-7977 inhibits the Hippo-YAP signaling pathway in bone marrow mesenchymal stromal cells. PLoS One. 2019; 14(3): e0213220.
  51. Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019; 20(3): 175–193.
  52. Qian S, Wei Z, Yang W, et al. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol. 2022; 12: 985363.
  53. Muenchow A, Weller S, Hinterleitner C, et al. The BCL-2 selective inhibitor ABT-199 sensitizes soft tissue sarcomas to proteasome inhibition by a concerted mechanism requiring BAX and NOXA. Cell Death Dis. 2020; 11(8): 701.
  54. Liao ZB, Tan XL, Dong KS, et al. miRNA-448 inhibits cell growth by targeting BCL-2 in hepatocellular carcinoma. Dig Liver Dis. 2019; 51(5): 703–711.
  55. Kaban K, Hinterleitner C, Zhou Y, et al. Therapeutic silencing of BCL-2 using NK cell-derived exosomes as a novel therapeutic approach in breast cancer. Cancers (Basel). 2021; 13(10).
  56. Di Martile M, Farini V, Consonni FM, et al. Melanoma-specific bcl-2 promotes a protumoral M2-like phenotype by tumor-associated macrophages. J Immunother Cancer. 2020; 8(1).
  57. Song S, Chen Q, Li Y, et al. Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma. Gut. 2021; 70(12): 2238–2248.
  58. Henriet P, Emonard H. Matrix metalloproteinase-2: Not (just) a "hero" of the past. Biochimie. 2019; 166: 223–232.
  59. Gonzalez-Avila G, Sommer B, Mendoza-Posada DA, et al. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019; 137: 57–83.
  60. Ratajczak-Wielgomas K, Kmiecik A, Dziegiel P. Role of periostin expression in non-small cell lung cancer: periostin silencing inhibits the migration and invasion of lung cancer cells via regulation of MMP-2 expression. Int J Mol Sci. 2022; 23(3).
  61. Zhao H, Xing F, Yuan J, et al. Sevoflurane inhibits migration and invasion of glioma cells via regulating miR-34a-5p/MMP-2 axis. Life Sci. 2020; 256: 117897.
  62. Gu Ye, Yu J, Ding C, et al. Flavonoid GL-V9 suppresses invasion and migration of human colorectal cancer cells by inhibiting PI3K/Akt and MMP-2/9 signaling. J Cancer. 2021; 12(15): 4542–4551.
  63. Huang CC, Wang PH, Lu YT, et al. Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma. Molecules. 2020; 25(20).

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