Nuclear Morphology and the Biology of Cancer Cells

Abstract

Background: For more than a century, diagnostic pathologists have used morphologic abnormalities of the nucleus as essential diagnostic features to distinguish benign from malignant cells. These features include nuclear enlargement and increased nuclear-to-cytoplasmic ratio, nuclear membrane irregularities, hyperchromasia, and abnormal chromatin distribution. As our knowledge about the genetic and epigenetic abnormalities of cancer cells has increased in recent decades, the pathophysiologic mechanisms that underlie these morphologic abnormalities remain incompletely understood. Summary: This review attempts to summarize biologic abnormalities in malignant cells related to these morphologic changes. The molecular anatomy of the nuclear envelope in normal and malignant cells is discussed as well as regulation of nuclear size and shape, regulation of signal transduction pathways by molecules of the nuclear envelope, chromatin distribution, and the effects of HPV infection on dysplastic cells in the uterine cervix. Key Message: Causes of morphologic nuclear abnormalities in malignant cells are likely multifactorial. They probably include mutations, dysregulation of signal transduction pathways, abnormal gene expression patterns, alterations of nuclear envelope proteins and chromatin, and aneuploidy.

A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality

“…This means that the corresponding yields for all normal human cells will be the same; of course, this does not happen in cancer cells which are characterized by an elevated mitotic index [102]. In this model, and in the case of cancer cells which are generally characterized by unregulated growth, and larger nuclei [103], by giving the corresponding measured values of the cell parameters N g and A n for every studied cell, we efficiently predict cell survival after their irradiation with heavy ions. In this way, we prove the model's adaptability to any alternation between normal and cancer cell lines, and vice versa.…”

UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues

“…However, only some cell types, epithelia in colorectal adenocarcinoma for example, exhibited the ring-like structure that is characteristic of nuclear lamina in cultured epithelial cells. The nuclear envelope in immune and other cells has folds and invaginations 23 and in our data, NES staining could be irregular and diffuse, further emphasizing the difficulty of finding a broadly useful NES stain in tissue.…”

Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation

“…Nuclear morphology is a common marker for cell determination and classification [ 28 , 29 ]. The nucleus can transpire defects depending of its cell state, aging, or upon mutations.…”

“…Morphological irregularities of the nucleus are not only a characteristic of aging and senescent cells but also a diagnostic factor for tumor cells ( Figure 3 A) [ 37 ]. Nuclear morphology allows the classification of cell states by pathologists [ 28 , 29 ], such as in the case of cervical cancer and the examination of cervical cells using the Papanicolaou smear test. In this test, progression toward cancer due to the infection with the Papilloma virus is characterized by a strident and folded nuclear envelope as well as the presence of micronuclei and multi-lobular nuclei [ 28 , 48 ].…”

“…Nuclear morphology allows the classification of cell states by pathologists [ 28 , 29 ], such as in the case of cervical cancer and the examination of cervical cells using the Papanicolaou smear test. In this test, progression toward cancer due to the infection with the Papilloma virus is characterized by a strident and folded nuclear envelope as well as the presence of micronuclei and multi-lobular nuclei [ 28 , 48 ]. Another example is the pancreatic ductal adenocarcinoma where during progression toward cancer, the nuclear membrane acquires an irregular shape, resulting in an enlarged nucleus and increased nucleus/cytoplasm ratio as well as the presence of macronucleoli [ 49 , 50 ].…”