The Stem Cell Phenotype of Aggressive Breast Cancer Cells
Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of onco...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-03-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/11/3/340 |
| _version_ | 1797705942129704960 |
|---|---|
| author | Naira V. Margaryan Hannah Hazard-Jenkins Mohamad A. Salkeni Matthew B. Smolkin James A. Coad Sijin Wen Elisabeth A. Seftor Richard E. B. Seftor Mary J. C. Hendrix |
| author_facet | Naira V. Margaryan Hannah Hazard-Jenkins Mohamad A. Salkeni Matthew B. Smolkin James A. Coad Sijin Wen Elisabeth A. Seftor Richard E. B. Seftor Mary J. C. Hendrix |
| author_sort | Naira V. Margaryan |
| collection | DOAJ |
| description | Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence. |
| first_indexed | 2024-03-12T05:43:48Z |
| format | Article |
| id | doaj.art-bf548a4c131e45e2a025c6679f99bff2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T05:43:48Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bf548a4c131e45e2a025c6679f99bff22023-09-03T05:46:50ZengMDPI AGCancers2072-66942019-03-0111334010.3390/cancers11030340cancers11030340The Stem Cell Phenotype of Aggressive Breast Cancer CellsNaira V. Margaryan0Hannah Hazard-Jenkins1Mohamad A. Salkeni2Matthew B. Smolkin3James A. Coad4Sijin Wen5Elisabeth A. Seftor6Richard E. B. Seftor7Mary J. C. Hendrix8Department of Biochemistry, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506, USADepartment of Biochemistry, West Virginia University, Morgantown, WV 26506, USADepartment of Biochemistry, West Virginia University, Morgantown, WV 26506, USADepartment of Biology, Shepherd University, Shepherdstown, WV 25443, USAAggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence.http://www.mdpi.com/2072-6694/11/3/340Nodalbreast cancerABCA1cancer stem cellsdoxorubicin/cyclophosphamide/taxanes (paclitaxel or docetaxel) (ACT)docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP)docetaxel/cyclophosphamide (TC) |
| spellingShingle | Naira V. Margaryan Hannah Hazard-Jenkins Mohamad A. Salkeni Matthew B. Smolkin James A. Coad Sijin Wen Elisabeth A. Seftor Richard E. B. Seftor Mary J. C. Hendrix The Stem Cell Phenotype of Aggressive Breast Cancer Cells Cancers Nodal breast cancer ABCA1 cancer stem cells doxorubicin/cyclophosphamide/taxanes (paclitaxel or docetaxel) (ACT) docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) docetaxel/cyclophosphamide (TC) |
| title | The Stem Cell Phenotype of Aggressive Breast Cancer Cells |
| title_full | The Stem Cell Phenotype of Aggressive Breast Cancer Cells |
| title_fullStr | The Stem Cell Phenotype of Aggressive Breast Cancer Cells |
| title_full_unstemmed | The Stem Cell Phenotype of Aggressive Breast Cancer Cells |
| title_short | The Stem Cell Phenotype of Aggressive Breast Cancer Cells |
| title_sort | stem cell phenotype of aggressive breast cancer cells |
| topic | Nodal breast cancer ABCA1 cancer stem cells doxorubicin/cyclophosphamide/taxanes (paclitaxel or docetaxel) (ACT) docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) docetaxel/cyclophosphamide (TC) |
| url | http://www.mdpi.com/2072-6694/11/3/340 |
| work_keys_str_mv | AT nairavmargaryan thestemcellphenotypeofaggressivebreastcancercells AT hannahhazardjenkins thestemcellphenotypeofaggressivebreastcancercells AT mohamadasalkeni thestemcellphenotypeofaggressivebreastcancercells AT matthewbsmolkin thestemcellphenotypeofaggressivebreastcancercells AT jamesacoad thestemcellphenotypeofaggressivebreastcancercells AT sijinwen thestemcellphenotypeofaggressivebreastcancercells AT elisabethaseftor thestemcellphenotypeofaggressivebreastcancercells AT richardebseftor thestemcellphenotypeofaggressivebreastcancercells AT maryjchendrix thestemcellphenotypeofaggressivebreastcancercells AT nairavmargaryan stemcellphenotypeofaggressivebreastcancercells AT hannahhazardjenkins stemcellphenotypeofaggressivebreastcancercells AT mohamadasalkeni stemcellphenotypeofaggressivebreastcancercells AT matthewbsmolkin stemcellphenotypeofaggressivebreastcancercells AT jamesacoad stemcellphenotypeofaggressivebreastcancercells AT sijinwen stemcellphenotypeofaggressivebreastcancercells AT elisabethaseftor stemcellphenotypeofaggressivebreastcancercells AT richardebseftor stemcellphenotypeofaggressivebreastcancercells AT maryjchendrix stemcellphenotypeofaggressivebreastcancercells |