RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells
Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological featu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/1/234 |
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| author | Yushu Gu Valentin Bobrin Dayong Zhang Bing Sun Chun Ki Ng Sung-Po R. Chen Wenyi Gu Michael J. Monteiro |
| author_facet | Yushu Gu Valentin Bobrin Dayong Zhang Bing Sun Chun Ki Ng Sung-Po R. Chen Wenyi Gu Michael J. Monteiro |
| author_sort | Yushu Gu |
| collection | DOAJ |
| description | Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological features, including therapeutic targets, difficult. The use of three-dimensional (3D) culture systems to enrich CSCs has some limitations, including low sphere forming efficiency, enzymatic digestion that may damage surface proteins, and more importantly no means to sustain the stem properties. A responsive 3D polymer extracellular matrix (ECM) system coated with RGD was used to enrich CSCs, sustain stemness and avoid enzymatic dissociation. RGD was used as a targeting motif and a ligand to bind integrin receptors. We found that the system was able to increase sphere forming efficiency, promote the growth of spheric cells, and maintain stemness-associated properties compared to the current 3D culture. We showed that continuous culture for three generations of colon tumour spheroid led to the stem marker CD24 gradually increasing. Furthermore, the new system could enhance the cancer cell sphere forming ability for the difficult triple negative breast cancer cells, MBA-MD-231. The key stem gene expression for colon cancer also increased with the new system. Further studies indicated that the concentration of RGD, especially at high doses, could inhibit stemness. Taken together, our data demonstrate that our RGD-based ECM system can facilitate the enrichment of CSCs and now allow for the investigation of new therapeutic approaches for colorectal cancer or other cancers. |
| first_indexed | 2024-03-11T10:06:19Z |
| format | Article |
| id | doaj.art-dbc8d936b80e4ce685538fca3b8910ef |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:06:19Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dbc8d936b80e4ce685538fca3b8910ef2023-11-16T15:03:26ZengMDPI AGCancers2072-66942022-12-0115123410.3390/cancers15010234RGD-Coated Polymer Nanoworms for Enriching Cancer Stem CellsYushu Gu0Valentin Bobrin1Dayong Zhang2Bing Sun3Chun Ki Ng4Sung-Po R. Chen5Wenyi Gu6Michael J. Monteiro7Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, QLD 4072, AustraliaCancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological features, including therapeutic targets, difficult. The use of three-dimensional (3D) culture systems to enrich CSCs has some limitations, including low sphere forming efficiency, enzymatic digestion that may damage surface proteins, and more importantly no means to sustain the stem properties. A responsive 3D polymer extracellular matrix (ECM) system coated with RGD was used to enrich CSCs, sustain stemness and avoid enzymatic dissociation. RGD was used as a targeting motif and a ligand to bind integrin receptors. We found that the system was able to increase sphere forming efficiency, promote the growth of spheric cells, and maintain stemness-associated properties compared to the current 3D culture. We showed that continuous culture for three generations of colon tumour spheroid led to the stem marker CD24 gradually increasing. Furthermore, the new system could enhance the cancer cell sphere forming ability for the difficult triple negative breast cancer cells, MBA-MD-231. The key stem gene expression for colon cancer also increased with the new system. Further studies indicated that the concentration of RGD, especially at high doses, could inhibit stemness. Taken together, our data demonstrate that our RGD-based ECM system can facilitate the enrichment of CSCs and now allow for the investigation of new therapeutic approaches for colorectal cancer or other cancers.https://www.mdpi.com/2072-6694/15/1/234RGDnano-wormCSCscancer stemnesscolon cancer |
| spellingShingle | Yushu Gu Valentin Bobrin Dayong Zhang Bing Sun Chun Ki Ng Sung-Po R. Chen Wenyi Gu Michael J. Monteiro RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells Cancers RGD nano-worm CSCs cancer stemness colon cancer |
| title | RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells |
| title_full | RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells |
| title_fullStr | RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells |
| title_full_unstemmed | RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells |
| title_short | RGD-Coated Polymer Nanoworms for Enriching Cancer Stem Cells |
| title_sort | rgd coated polymer nanoworms for enriching cancer stem cells |
| topic | RGD nano-worm CSCs cancer stemness colon cancer |
| url | https://www.mdpi.com/2072-6694/15/1/234 |
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