Rate of Growth:
Most benign grow slowly, most cancers grow much faster exceptions:
rate of growth of leiomyomas of uterus influenced by circulating levels of estrogens (may incr rapidly during pregnancy and then cease growing, becoming largely fibrocalcific, after menopause)
Adenomas of pituitary gland locked into sella turcica shrink suddenly (undergo a wave of necrosis as progressive enlargement compresses their blood supply)
most benign incr in size slowly over span of m-yrs; malignant rate u. correlates inversely w/ level of diff
wide variation in rate of growth. Some grow slowly for yrs then enter a phase of rapid growth (emergence of an aggressive subclone of transformed cells)
Others grow relatively slowly and steadily; exceptional instances, growth may come almost to a standstill.
Even more exceptionally, some primary tumors (partic choriocarcinomas) may become totally necrotic, leaving only secondary metastatic implants.
most cancers progressively enlarge over time; most if not all cancers take yrs + sometimes decades to evolve into clinically overt lesions (“acute” childhood leukemias, initiate during fetal development yet manifest as fullblown cancers yrs later)
Rapidly growing malignant tumors often contain central areas of ischemic necrosis, bc blood supply fails to keep pace
Cancer Stem Cells and Lineages: continued growth + maintenance of many tissues that contain short-lived cells, such as formed elements of blood + epith cells of GI tract and skin, require a resident population of tissue stem cells that are long-lived and capable of self-renewal. Tissue stem cells rare + exist in a niche created by support cells, which produce paracrine factors that sustain the stem cells. Cancers are immortal and have limitless proliferative capacity--> also must contain cells w/ “stem-like” properties. cancer stem cell hypothesis: only a special subset of cells within tumors has capacity for self-renewal; like normal stem cells, cancer stem cells are resistant to conventional therapies, because of their low rate of cell division + expression of factors, such as multiple drug resistance1 (MDR1), that counteract effects of chemotherapeutic drugs. Cancer stem cells could arise from normal tissue stem cells or from more differentiated cells that, as part of the transformation process, acquire property of self-renewal. Studies of certain leukemias suggest that both possibilities occur, in that CML originates from malignant counterpart of a normal HSC, whereas certain acute myeloid (myelogenous) leukemias are derived from more differentiated myeloid precursors