Organotropism: new insights into molecular mechanisms of breast cancer metastasis

Abstract

Metastasis accounts for 90% of breast cancer mortality. Despite the significant progress made over the past decade in cancer medicine our understanding of metastasis remains limited, therefore preventing and targeting metastasis is not yet possible. Breast cancer cells preferentially metastasize to specific organs, known as “organotropic metastasis”, which is regulated by subtypes of breast cancer, host organ microenvironment, and cancer cells-organ interactions. The cross-talk between cancer cells and host organs facilitates the formation of the premetastatic niche and is augmented by factors released from cancer cells prior to the cancer cells’ arrival at the host organ. Moreover, host microenvironment and specific organ structure influence metastatic niche formation and interactions between cancer cells and local resident cells, regulating the survival of cancer cells and formation of metastatic lesions. Understanding the molecular mechanisms of organotropic metastasis is essential for biomarker-based prediction and prognosis, development of innovative therapeutic strategy, and eventual improvement of patient outcomes. In this review, we summarize the molecular mechanisms of breast cancer organotropic metastasis by focusing on tumor cell molecular alterations, stemness features, and cross-talk with the host environment. In addition, we also update some new progresses on our understanding about genetic and epigenetic alterations, exosomes, microRNAs, circulating tumor cells and immune response in breast cancer organotropic metastasis.

In search of the altering salivary proteome in metastatic breast and ovarian cancers

“…31 An important aspect that has been relatively unexplored is the use of potential markers to better understand metastatic organotropic behavior of breast and ovarian cancers, which has an incidence rate of 15%-30%. 8,14,16 Although, early prediction of organotropism can decrease the incidence of cancer-related mortality in women, these clinical methods are invasive and expensive. 8,14,16 Although, early prediction of organotropism can decrease the incidence of cancer-related mortality in women, these clinical methods are invasive and expensive.…”

“…3 Currently, BRCA1/2 mutation, PTEN, and p53 analysis are being studied to uncover organotropism including predictive analysis of HRs to investigate the molecular subtype of breast and ovarian cancers that can metastasize to distant organs using immunohistochemical staining or microarrays. 8,14,16 Although, early prediction of organotropism can decrease the incidence of cancer-related mortality in women, these clinical methods are invasive and expensive. 32 Similarly, neoadjuvant chemotherapy of sensitive/resistant proteins has been studied to determine effective treatments.…”

“…6 Cancer metastasis to distant organs and their late-stage detection are the major cause of mortality in females with breast and ovarian cancers. 8,9 According to the American Cancer Society, the most common type of breast cancer is ductal carcinoma, and lobular carcinoma, which has a 30% probability of spreading to the ovary, is the common type of ovarian cancer. 7 In breast cancer, invasive ductal carcinoma (IDC), and in ovarian cancer, serous ovarian carcinoma (SOC), are the most frequent and aggressive histological type of cancer metastasizing to different organs.…”

“…7 In breast cancer, invasive ductal carcinoma (IDC), and in ovarian cancer, serous ovarian carcinoma (SOC), are the most frequent and aggressive histological type of cancer metastasizing to different organs. 8,9 According to the American Cancer Society, the most common type of breast cancer is ductal carcinoma, and lobular carcinoma, which has a 30% probability of spreading to the ovary, is the common type of ovarian cancer. 10 In addition, depending on the breast cancer molecular subtype, it can spread to different organs such as bones, brain, lungs, and the liver.…”

“…10 In addition, depending on the breast cancer molecular subtype, it can spread to different organs such as bones, brain, lungs, and the liver. 8 Similarly, ovarian cancer has the potential to spread to the abdominal region, and in some cases, to the breast. 11 However, de novo breast and ovarian cancer metastases, which could depend on the intrinsic properties of both malignant cells and microenvironment of metastasis-susceptible organ, has also been reported in some cases before the primary diagnosis of cancer.…”