Q. My professor asked this on an exam: What’s the difference in molecular mechanism between metaplasia and neoplasia?


A. Metaplasia is the changing of one cell type to another. The term is used most often in reference to epithelial cells, for example, when the normal glandular epithelium of the cervix is replaced with squamous epithelium, it is called “squamous metaplasia”. It simply means that the basal cells (the stem cells of the epithelial layer) switch from making one type of epithelial cell to another.


Though it is not malignant or even premalignant, in and of itself, metaplasia sometimes indicates that there has been damage to the area, and if the insult continues, dysplasia or even frank malignancy can occur. This is fairly common in the lung: metaplasia of the bronchial epithelium is followed by dysplasia, which is followed by carcinoma. The molecular mechanisms of this whole process of metaplasia are not well understood.


“Neoplasia” literally means “new growth.” Neoplastic cells have several characteristics that make them nasty: they grow autonomously without any need for growth signals, they are insensitive to normal growth-inhibitory signals, they don’t die off like they should, they are capable of limitless replication, and – if they are malignant neoplastic cells – they invade vessels and travel to different parts of the body and set up shop.


There are lots of molecular mechanisms (and corresponding genetic mutations) that underlie these neoplastic qualities; most neoplasms have several such mutations. A cancer cell can have mutations in many different genes – for example, the genes encoding growth factor receptors, signal-transducing proteins, nuclear transcription factors, or cyclins.


Sometimes these mutations turn on a gene that promotes growth. The normal variants of these growth-promoting genes are called “proto-oncogenes” and the mutated variants are called “oncogenes.” An example of just such a gene is the RAS proto-oncogene, which makes a signal transduction protein involved in cell growth. Many neoplasms have a mutated RAS gene (called the RAS oncogene) that has been altered in such a way that it is always turned on. Which means that the cells containing the mutation are always transducing growth signals, and always growing and dividing.


Another type of mutation can occur in genes (called “tumor suppressor genes”) that normally put brakes on cell growth. An example of this type of gene is the retinoblastoma tumor-suppressor gene, which normally stops cells at the G1 checkpoint in the cell cycle. In certain tumors, the retinoblastoma gene is mutated in such a way that it doesn’t work. Cells that have this mutated gene proceed without pause through the G1 checkpoint, heading full-tilt on to mitosis.


So, to summarize: the molecular mechanisms of metaplasia are not well understood. The molecular mechanisms underlying neoplasia are numerous and complex.