ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer.
Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4569358?pdf=render |
| _version_ | 1819240029000564736 |
|---|---|
| author | Thierry Jardé Lisa Kass Margaret Staples Helen Lescesen Peter Carne Karen Oliva Paul J McMurrick Helen E Abud |
| author_facet | Thierry Jardé Lisa Kass Margaret Staples Helen Lescesen Peter Carne Karen Oliva Paul J McMurrick Helen E Abud |
| author_sort | Thierry Jardé |
| collection | DOAJ |
| description | Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts. |
| first_indexed | 2024-12-23T14:01:31Z |
| format | Article |
| id | doaj.art-111cb834b2f44a5ebc20762dc102661a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:01:31Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-111cb834b2f44a5ebc20762dc102661a2022-12-21T17:44:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013833610.1371/journal.pone.0138336ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer.Thierry JardéLisa KassMargaret StaplesHelen LescesenPeter CarneKaren OlivaPaul J McMurrickHelen E AbudSeveral studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.http://europepmc.org/articles/PMC4569358?pdf=render |
| spellingShingle | Thierry Jardé Lisa Kass Margaret Staples Helen Lescesen Peter Carne Karen Oliva Paul J McMurrick Helen E Abud ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. PLoS ONE |
| title | ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. |
| title_full | ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. |
| title_fullStr | ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. |
| title_full_unstemmed | ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. |
| title_short | ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. |
| title_sort | erbb3 positively correlates with intestinal stem cell markers but marks a distinct non proliferative cell population in colorectal cancer |
| url | http://europepmc.org/articles/PMC4569358?pdf=render |
| work_keys_str_mv | AT thierryjarde erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT lisakass erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT margaretstaples erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT helenlescesen erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT petercarne erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT karenoliva erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT pauljmcmurrick erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer AT heleneabud erbb3positivelycorrelateswithintestinalstemcellmarkersbutmarksadistinctnonproliferativecellpopulationincolorectalcancer |