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 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

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 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

Global retrieval of stratospheric and tropospheric BrO columns from the Ozone Mapping and Profiler Suite Nadir Mapper (OMPS-NM) on board the Suomi-NPP satellite

Quantifying the global bromine monoxide (BrO) budget is essential to understand ozone chemistry better. In particular, the tropospheric BrO budget has not been well characterized. Here, we retrieve nearly a decade (February 2012–July 2021) of stratospheric and tropospheric BrO vertical columns from the Ozone Mapping and Profiling Suite Nadir Mapper (OMPS-NM) on board the Suomi National Polar-orbiting Partnership (Suomi-NPP) satellite. In quantifying tropospheric BrO enhancements from total slant columns, the key aspects involve segregating them from stratospheric enhancements and applying appropriate air mass factors. To address this concern and improve upon the existing methods, our study proposes an approach that applies distinct BrO vertical profiles based on the presence or absence of tropospheric BrO enhancement at each pixel, identifying it dynamically using a satellite-derived stratospheric-ozone–BrO relationship. We demonstrate good agreement for both stratosphere (r = 0.81–0.83) and troposphere (r = 0.50–0.70) by comparing monthly mean BrO vertical columns from OMPS-NM with ground-based observations from three stations (Lauder, Utqiaġvik, and Harestua). Although algorithm performance is primarily assessed at high latitudes, the OMPS-NM BrO retrievals successfully capture tropospheric enhancements not only in polar regions but also in extrapolar areas, such as the Rann of Kutch and the Great Salt Lake. We also estimate random uncertainties in the retrievals pixel by pixel, which can assist in quantitative applications of the OMPS-NM BrO dataset. Our BrO retrieval algorithm is designed for cross-sensor applications and can be adapted to other space-borne ultraviolet spectrometers, contributing to the creation of continuous long-term satellite BrO observation records.</p

Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

Organotypic modelling as a means of investigating epithelial-stromal interactions during tumourigenesis

The advent of co-culture approaches has allowed researchers to more accurately model the behaviour of epithelial cells in cell culture studies. The initial work on epidermal modelling allowed the development of reconstituted epidermis, growing keratinocytes on top of fibroblasts seeded in a collagen gel at an air-liquid interface to generate terminally differentiated 'skin equivalents'. In addition to developing ex vivo skin sheets for the treatment of burns victims, such cultures have also been used as a means of investigating both the development and repair of the epidermis, in more relevant conditions than simple two-dimensional culture, but without the use of animals. More recently, by varying the cell types used and adjusting the composition of the matrix components, this physiological system can be adapted to allow the study of interactions between tumour cells and their surrounding stroma, particularly with regards to how such interactions regulate invasion. Here we provide a summary of the major themes involved in tumour progression and consider the evolution of the approaches used to study cancer cell behaviour. Finally, we review how organotypic models have facilitated the study of several key pathways in cancer development and invasion, and speculate on the exciting future roles for these models in cancer research