Implications of Hypoxia in Breast Cancer Metastasis to Bone

Abstract

Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells. Patients, whose primary tumor biopsies show high HIF expression levels, have a greater risk of metastasis. The current review will highlight the potential role of hypoxia in breast cancer metastasis to the bone by considering the regulation of many steps in the metastatic process that include invasion, migration, margination and extravasation, as well as homing signals and regulation of the bone microenvironment.

Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis

“…The environment is associated with poor survival and increased metastatic incidence and tumor burden in patients with various cancer, including HNC, prostate cancer, cervical cancer, breast cancer, etc. 95 – 97 Under low oxygen tensions, cancer cells have predilection for becoming invasive and disseminating to distant sites through hypoxia-associated transcriptional activation, including the hypoxia-inducible factor (HIF), transcriptional regulators, mTOR complex 1, autophagy and endoplasmic reticulum stress responses, etc. 98 , 99 Also, it is increasingly suggested that hypoxia is responsible for therapeutic resistance to both chemotherapy and radiotherapy because cancer cells may remain a state of dormancy or growth arrest in such microenvironment.…”

RhoB is regulated by hypoxia and modulates metastasis in breast cancer

“…The presence of intratumoral hypoxia, or reduced O 2 availability, is associated with an increased risk of invasion and metastasis and therefore an overall worse patient prognosis. 39,40 In renal carcinoma cells (Caki-1), RhoB protein expression was unaffected by exposure to less than 6 hours of hypoxia. 34 In a glioblastoma cell line (U87 cells), hypoxia did not alter the levels of RhoB but did enhance RhoB activation (GTP-bound RhoB).…”

Pretreatment Variations in Haematological Parameters of Breast Cancer Patients

“…Haematopoiesis suppression due to metastasis of breast cancer cells to bone marrow has already been described [25,26]. On the other hand, low Hb level has been shown to cause poorer oxygenation of tumor cells, which could activate the metastatic genes, leading to the metastasis and resistance of cancer cells to chemo and radiotherapy, resulting in the worse survival of BC patients [12][13]. Hence, Hb is an important parameter, which may be improved in these patients, for example through the exogenous administration of erythropoietin [27].…”

“…Many studies have shown the adverse outcome of malignancies in the patients who have poor haematological parameters. The Hb [12,13], ESR level [14], and the white blood cell (WBC) counts, including full and differential [15][16][17], predict the severity and mortality risk of cancer patients. Platelet count aids to monitor the progress of cancer.…”