Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Short Communication

Micro-fragmented Fat Inhibits the Progression of Human Mesothelioma Xenografts in Mice

Author(s): Silvia La Monica, Valentina Coccé, Mara Bonelli*, Giulio Alessandri, Roberta Alfieri, Costanza Annamaria Lagrasta, Caterina Frati, Lisa Flammini, Aldo Gianni, Francesco Petrella, Francesca Paino and Augusto Pessina

Volume 23, Issue 8, 2023

Published on: 17 May, 2023

Page: [663 - 668] Pages: 6

DOI: 10.2174/1568009623666230201092302

Price: $65

conference banner
Abstract

Background: Malignant pleural mesothelioma is a pathology with no effective therapy and a poor prognosis. Our previous study demonstrated an in vitro inhibitory effect on mesothelioma cell lines of both the lysate and secretome of adipose tissue-derived Mesenchymal Stromal Cells. The inhibitory activity on tumor growth has been demonstrated also in vivo: five million Mesenchymal Stromal Cells, injected “in situ”, produced a significant therapeutic efficacy against MSTO-211H xenograft equivalent to that observed after the systemic administration of paclitaxel.

Objective: The objective of this study is to evaluate the efficacy of low amount (half a million) Mesenchymal Stromal Cells and micro-fragmented adipose tissues (the biological tissue from which the Mesenchymal Stromal Cells were isolated) on mesothelioma cells growth.

Methods: Tumor cells growth inhibition was evaluated in vitro and in a xenograft model of mesothelioma.

Results: The inhibitory effect of micro-fragmented fat from adipose-tissue has been firstly confirmed in vitro on MSTO-211H cell growth. Then the efficacy against the growth of mesothelioma xenografts in mice of both micro-fragmented fat and low amount of Mesenchymal Stromal Cells has been evaluated. Our results confirmed that both Mesenchymal Stromal Cells and micro-fragmented fat, injected “in situ”, did not stimulate mesothelioma cell growth. By contrast, micro-fragmented fat produced a significant inhibition of tumor growth and progression, comparable to that observed by the treatment with paclitaxel. Low amount of Mesenchymal Stromal Cells exerted only a little anticancer activity.

Conclusion: Micro-fragmented fat inhibited mesothelioma cell proliferation in vitro and exerted a significant control of the mesothelioma xenograft growth in vivo.

Keywords: Mesothelioma, micro-fragmented fat, mesenchymal stromal cells, paclitaxel, xenograft, adipose tissue.

« Previous
Graphical Abstract
[1]
Carbone, M.; Ly, B.H.; Dodson, R.F.; Pagano, I.; Morris, P.T.; Dogan, U.A.; Gazdar, A.F.; Pass, H.I.; Yang, H. Malignant mesothelioma: facts, myths, and hypotheses. J. Cell. Physiol., 2012, 227(1), 44-58.
[http://dx.doi.org/10.1002/jcp.22724] [PMID: 21412769]
[2]
Mutti, L.; Peikert, T.; Robinson, B.W.S.; Scherpereel, A.; Tsao, A.S.; de Perrot, M.; Woodard, G.A.; Jablons, D.M.; Wiens, J.; Hirsch, F.R.; Yang, H.; Carbone, M.; Thomas, A.; Hassan, R. Scientific advances and new frontiers in mesothelioma therapeutics. J. Thorac. Oncol., 2018, 13(9), 1269-1283.
[http://dx.doi.org/10.1016/j.jtho.2018.06.011] [PMID: 29966799]
[3]
Li, G.C.; Zhang, H.W.; Zhao, Q.C.; Sun, L.; Yang, J.J.; Hong, L.; Feng, F.; Cai, L. Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor β1. Oncol. Lett., 2016, 11(2), 1089-1094.
[http://dx.doi.org/10.3892/ol.2015.3997] [PMID: 26893697]
[4]
Ayuzawa, R.; Doi, C.; Rachakatla, R.S.; Pyle, M.M.; Maurya, D.K.; Troyer, D.; Tamura, M. Naïve human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer Lett., 2009, 280(1), 31-37.
[http://dx.doi.org/10.1016/j.canlet.2009.02.011] [PMID: 19285791]
[5]
Cortes-Dericks, L.; Froment, L.; Kocher, G.; Schmid, R.A. Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. Stem Cell Res. Ther., 2016, 7(1), 25.
[http://dx.doi.org/10.1186/s13287-016-0282-7] [PMID: 26861734]
[6]
Coccè, V.; La Monica, S.; Bonelli, M.; Alessandri, G.; Alfieri, R.; Lagrasta, C.A.; Madeddu, D.; Frati, C.; Flammini, L.; Lisini, D.; Marcianti, A.; Parati, E.; Paino, F.; Giannì, A.; Farronato, G.; Falco, A.; Spaggiari, L.; Petrella, F.; Pessina, A. Inhibition of human malignant pleural mesothelioma growth by mesenchymal stromal Cells. Cells, 2021, 10(6), 1427.
[http://dx.doi.org/10.3390/cells10061427] [PMID: 34201002]
[7]
Bepler, G.; Koehler, A.; Kiefer, P.; Havemann, K.; Beisenherz, K.; Jaques, G.; Gropp, C.; Haeder, M. Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines. Differentiation, 1988, 37(2), 158-171.
[http://dx.doi.org/10.1111/j.1432-0436.1988.tb00806.x] [PMID: 2840315]
[8]
Alessandri, G.; Coccè, V.; Pastorino, F.; Paroni, R.; Dei Cas, M.; Restelli, F.; Pollo, B.; Gatti, L.; Tremolada, C.; Berenzi, A.; Parati, E.; Brini, A.T.; Bondiolotti, G.; Ponzoni, M.; Pessina, A. Microfragmented human fat tissue is a natural scaffold for drug delivery: Potential application in cancer chemotherapy. J. Control. Release, 2019, 302, 2-18.
[http://dx.doi.org/10.1016/j.jconrel.2019.03.016] [PMID: 30890444]
[9]
Ceserani, V.; Ferri, A.; Berenzi, A.; Benetti, A.; Ciusani, E.; Pascucci, L.; Bazzucchi, C.; Coccè, V.; Bonomi, A.; Pessina, A.; Ghezzi, E.; Zeira, O.; Ceccarelli, P.; Versari, S.; Tremolada, C.; Alessandri, G. Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vasc. Cell, 2016, 8(1), 3.
[http://dx.doi.org/10.1186/s13221-016-0037-3] [PMID: 27547374]
[10]
La Monica, S.; Cretella, D.; Bonelli, M.; Fumarola, C.; Cavazzoni, A.; Digiacomo, G.; Flammini, L.; Barocelli, E.; Minari, R.; Naldi, N.; Petronini, P.G.; Tiseo, M.; Alfieri, R. Trastuzumab emtansine delays and overcomes resistance to the third-generation EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines. J. Exp. Clin. Cancer Res., 2017, 36(1), 174.
[http://dx.doi.org/10.1186/s13046-017-0653-7] [PMID: 29202823]
[11]
La Monica, S.; Minari, R.; Cretella, D.; Flammini, L.; Fumarola, C.; Bonelli, M.; Cavazzoni, A.; Digiacomo, G.; Galetti, M.; Madeddu, D.; Falco, A.; Lagrasta, C.A.; Squadrilli, A.; Barocelli, E.; Romanel, A.; Quaini, F.; Petronini, P.G.; Tiseo, M.; Alfieri, R. Third generation EGFR inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in EGFR-mutated pre-clinical models of NSCLC. J. Exp. Clin. Cancer Res., 2019, 38(1), 222.
[http://dx.doi.org/10.1186/s13046-019-1240-x] [PMID: 31138260]
[12]
Antunes, P.; Cruz, A.; Barbosa, J.; Bonifácio, V.D.B.; Pinto, S.N. Lipid droplets in cancer: From composition and role to imaging and therapeutics. Molecules, 2022, 27(3), 991.
[http://dx.doi.org/10.3390/molecules27030991] [PMID: 35164256]
[13]
Cruz, A.L.S.; Barreto, E.A.; Fazolini, N.P.B.; Viola, J.P.B.; Bozza, P.T. Lipid droplets: platforms with multiple functions in cancer hallmarks. Cell Death Dis., 2020, 11(2), 105.
[http://dx.doi.org/10.1038/s41419-020-2297-3] [PMID: 32029741]
[14]
Abedin, M.R.; Barua, S. Isolation and purification of glycoglycerolipids to induce apoptosis in breast cancer cells. Sci. Rep., 2021, 11(1), 1298.
[http://dx.doi.org/10.1038/s41598-020-80484-x] [PMID: 33446783]
[15]
Zhai, L.; Sun, N.; Han, Z.; Jin, H.; Zhang, B. Liposomal short-chain C6 ceramide induces potent anti-osteosarcoma activity in vitro and in vivo. Biochem. Biophys. Res. Commun., 2015, 468(1-2), 274-280.
[http://dx.doi.org/10.1016/j.bbrc.2015.10.113] [PMID: 26505795]
[16]
Choi, M.K.; Song, I.S. Recent advances in the formulation of sphingolipid anticancer therapeutics. J. Pharm. Investig., 2020, 50(3), 295-307.
[http://dx.doi.org/10.1007/s40005-020-00475-y]
[17]
Lin, I.L.; Chou, H.L.; Lee, J.C.; Chen, F.W.; Fong, Y.; Chang, W.C.; Huang, H.W.; Wu, C.Y.; Chang, W.T.; Wang, H.M.D.; Chiu, C.C. The antiproliferative effect of C2-ceramide on lung cancer cells through apoptosis by inhibiting Akt and NFκB. Cancer Cell Int., 2014, 14(1), 1.
[http://dx.doi.org/10.1186/1475-2867-14-1] [PMID: 24393431]
[18]
Huang, W.C.; Chen, C.L.; Lin, Y.S.; Lin, C.F. Apoptotic sphingolipid ceramide in cancer therapy. J. Lipids, 2011, 2011, 565316.
[http://dx.doi.org/10.1155/2011/565316] [PMID: 21490804]
[19]
Jóźwiak, M.; Filipowska, A.; Fiorino, F.; Struga, M. Anticancer activities of fatty acids and their heterocyclic derivatives. Eur. J. Pharmacol., 2020, 871, 172937.
[http://dx.doi.org/10.1016/j.ejphar.2020.172937] [PMID: 31958454]
[20]
Liang, T.; Wen, D.; Chen, G.; Chan, A.; Chen, Z.; Li, H.; Wang, Z.; Han, X.; Jiang, L.; Zhu, J.J.; Gu, Z. Adipocyte‐derived anticancer lipid droplets. Adv. Mater., 2021, 33(26), 2100629.
[http://dx.doi.org/10.1002/adma.202100629] [PMID: 33987883]
[21]
Wen, D.; Wang, J. Adipocytes as anticancer. Matter, 2019, 1(5), 1203-1214.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy